Trace Element Concentration in the Blood and Aqueous Humor of Subjects with Eye Cataract.

Cataract, characterized by the opacification of the lens, is the leading cause of reversible blindness and visual impairment globally. The study aims to investigate the role of trace elements such as Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn in the development and severity of cataract. Elements were quantified by inductively coupled plasma mass spectrometry in blood and aqueous humor of 32 cataract cases and 27 controls living in the Latium region, Italy. The association between element concentration in blood and aqueous humor and cataract severity, gender, and age of subjects were also assessed. Results showed Cr levels significantly elevated in both blood and aqueous humor of cataract cases, with concentrations that increased with cataract severity. In addition, blood Pb levels were significantly higher in older cases and positively correlated with the age of cataract cases, while blood Co and Cu levels negatively correlated with cataract severity, suggesting changes in the levels of these elements. In conclusion, this study provides evidence of the involvement of specific elements in cataract development and severity, and the findings highlighted important avenues for future research. Understanding the biological mechanism underlying element-induced cataract may contribute to preventing cataractogenesis and providing targeted interventions.

Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

OBJECTIVES: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). METHODS: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. RESULTS: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. CONCLUSION: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

Alteration Ocular Motility in Retinitis Pigmentosa: Case-Control Study.

Purpose: To evaluate ocular motility (OM) disorders and strabismus in a sample of patients with retinitis pigmentosa (RP) and a control sample. Methods: In this cross-sectional retrospective analysis, we studied a sample of RP patients with a mean age of 48.74 years and an average visual acuity of 7/10 based on Snellen optotype and a sample of control patients with similar mean age (49 years [men], 47 years [women]) and sex and an average visual acuity of 9.9/10, with the aim of assessing correlations between alteration of OM and strabismus in RP patients based on age, high refractive defect, or severely impaired binocular vision. The examination followed a protocol of testing for anamnesis and best-corrected visual acuity, as well as a complete eye examination, corneal reflex, cover test, OM, Hess screen, and Lang test. Results: At the first orthoptic evaluation, 45.16% of patients showed strabismus, 41.93% exotropia (25% of cases intermittent), 3.22% esotropia, and 6.45% vertical deviation. Later evaluation showed strabismus in 25.80% of patients, exotropia in 19.35% (9.67% intermittent), esotropia in 3.22%, and vertical deviation in 3.22%. Assessment of eye motility study showed 51.6% overaction of the inferior oblique and hypofunction of the superior rectus, and 18% overaction of the lateral rectus and hypofunction of the medial rectus. According to our results, alterations in OM and strabismus in RP patients are not correlated with age or high refractive defect. Therefore, motility disorders and strabismus are attributed to a genetic factor to which men are more susceptible. Conclusion: The incidence of OM disorder was 77.42%, and strabismus was present in 45.16% of patients.

Topical antibiotic prophylaxis before intravitreal injections: a pilot study.

PURPOSE: To explore whether topical antibiotic prophylaxis in patients scheduled for intravitreal injections achieves surface sterility in a greater proportion of subjects as compared to povidone-iodine alone. MATERIAL AND METHODS: A randomized, triple-blind clinical trial. POPULATION: patients scheduled for intravitreal injections for maculopathy. INCLUSION CRITERIA: any sex and race, age 18 years and above. Subjects were randomized into 4 groups: the first group applied chloramphenicol (CHLORAM), the second netilmicin (NETILM), the third a commercial ozonized antiseptic solution (OZONE), and the fourth applied no drops (CONTROL). OUTCOME VARIABLE: percentage of non-sterile conjunctival swabs. Specimens were collected before and after the application of 5% povidone-iodine moments before the injection. RESULTS: Ninety-eight subjects (33.7% females, 64.3% males), mean age: 70.2 ± 9.3 years (54-91). Before povidone-iodine, both the CHLORAM and NETILM group showed a lower percentage of non-sterile swabs (61.1% and 31.3% respectively), as compared to the OZONE (83.3%) and CONTROL (86.5%) groups (p < .04). However, this statistical difference was lost after the application of povidone-iodine for 3 min. Percentage of non-sterile swabs in each group after applying 5% povidone-iodine: CHLORAM 11.1%, NETILM 12.5%, CONTROL 15.4%, OZONE 25.0%. This was not statistically significant (p > .05). CONCLUSIONS: Topical antibiotic prophylaxis with chloramphenicol or netilmicin drops decreases the bacterial load on the conjunctiva. However, after the application of povidone-iodine, all groups showed a significant reduction in the percentage of non-sterile swabs, and this value was comparable among all groups. For this reason, authors conclude that povidone-iodine alone is sufficient and prior topical antibiotic prophylaxis is not indicated.

Effect of COVID-19 lockdown on refractive errors in Italian children aged 5-12 years: A multi-center retrospective study.

PURPOSE: to explore the potential consequences of the COVID-19 lockdown on the prevalence of myopia among Italian children aged 5-12 years. MATERIALS AND METHODS: retrospective multicenter study conducted in Italy. Population: children aged 5-12. Selection: random selection of children who received an eye exam between 2016 to 2021. Inclusion criteria: healthy children presenting for a routine eye exam. Exclusion criteria: presence of ocular comorbidities other than refractive error, such as blepharoptosis, media opacities, corneal or retinal dystrophies, strabismus, amblyopia, or concurrent therapy with atropine 0.01%. Outcome measure: age and spherical equivalent (SE) measured in diopters (D) in the right eye (RE) in cycloplegia. Statistical analysis: ANOVA test. RESULTS: total of 803 children. In the years prior to COVID-19, the mean SE ± SD of healthy age-school children was: 0.54 ± 1.49 D in 2016; 0.43 ± 1.84 D in 2017; 0.34 ± 1.41 D in 2018; 0.35 ± 1.75 D in 2019 (ANOVA, p = .659). In 2021, the mean SE changed to -0.08 ± 1.44 D (ANOVA, p = .005). Mean age was comparable in all groups (ANOVA, p = .307). The prevalence of myopes (SE ≤-0.5D) and hyperopes (SE ≥ 2D) was respectively 24.10% and 9.64% among children aged 60-96 months, and 63.86% and 6.02% among children aged 97-144 months. These values represent a statistically-significant increase in the number of myopes (Chi-square, p = .016) and decrease in the number of hyperopes (Chi-square, p = .001), as compared to previous years (.06 and.48 respectively). CONCLUSION: this retrospective study shows a statistically-significant decrease in the mean SE in children aged 5-12 in the year following the COVID-19 lockdown. The percentage of myopes has increased significantly, while the percentage of hyperopes has decreased. The lifestyle changes caused by the lockdown led children to spend more time on near-work activities and digital devices, and less time outdoors. These are known risk factors for the development and progression of myopia. Studies in different countries are encouraged.

Quantification of Carbonic Anhydrase Inhibitors and Metabolites in Urine and Hair of Patients and Their Relatives.

Carbonic anhydrase inhibitors (CAIs) are prescription drugs also used in doping to dilute urine samples and tamper with urinalyses. Dorzolamide, brinzolamide, and acetazolamide are prohibited by the World Anti-Doping Agency. Detecting CAIs and their metabolites in biological samples is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment for ocular hypertension or glaucoma. Samples of the patients' relatives were analyzed to assess potential for accidental exposure. After washing, 25 mg hair was incubated with an acidic buffer at 100 °C for 1 h. After cooling and centrifugation, the supernatant was analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Urine (100 µL) was diluted and centrifuged before UHPLC-MS/MS analysis. Run time was 8 min through a reverse-phase column with a mobile phase gradient. MS/MS analysis was performed in a multiple-reaction monitoring mode after positive electrospray ionization. Median urinary concentration was 245 ng/mL (IQR: 116.2-501 ng/mL) for dorzolamide, 81.1 ng/mL (IQR: 35.9-125.3 ng/mL) for N-deethyl-dorzolamide, 0.77 ng/mL (IQR: 0.64 ng/mL-0.84 ng/mL) for N-acetyl-dorzolamide, 38.9 ng/mL (IQR: 20.4-79.2 ng/mL) for brinzolamide, and 72.8 ng/mL (IQR: 20.7-437.3 ng/mL) for acetazolamide. Median hair concentration was 0.48 ng/mg (IQR: 0.1-0.98 ng/mg) for dorzolamide, 0.07 ng/mg (IQR: 0.06-0.08 ng/mg) for N-deethyl-dorzolamide, 0.40 ng/mL (IQR: 0.13-1.95 ng/mL) for brinzolamide. Acetazolamide was detected in only one hair sample. Dorzolamide and brinzolamide were detected in the urine of three and one relatives, respectively. Cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. We reported the first concentrations of brinzolamide in hair.

Bovine Serum Amine Oxidase and Polyamine Analogues: Chemical Synthesis and Biological Evaluation Integrated with Molecular Docking and 3-D QSAR Studies.

Natural polyamines (PAs) are key players in cellular homeostasis by regulating cell growth and proliferation. Several observations highlight that PAs are also implicated in pathways regulating cell death. Indeed, the PA accumulation cytotoxic effect, maximized with the use of bovine serum amine oxidase (BSAO) enzyme, represents a valuable strategy against tumor progression. In the present study, along with the design, synthesis, and biological evaluation of a series of new spermine (Spm) analogues (1-23), a mixed structure-based (SB) and ligand-based (LB) protocol was applied. Binding modes of BSAO-PA modeled complexes led to clarify electrostatic and steric features likely affecting the BSAO-PA biochemical kinetics. LB and SB three-dimensional quantitative structure-activity relationship (Py-CoMFA and Py-ComBinE) models were developed by means of the 3d-qsar.com portal, and their analysis represents a strong basis for future design and synthesis of PA BSAO substrates for potential application in oxidative stress-induced chemotherapy.

Effects of Photo-Biomodulation in Stargardt Disease.

PURPOSE: Stargardt disease (STGD1) is the most common hereditary macular degeneration and currently no treatments have been approved to interrupt the progression of the disease. The aim of this study was to evaluate the efficacy of photo-biomodulation in patients with Stargardt disease 1 year after treatment, considering as primary outcomes improvements in best corrected visual acuity (BCVA), microperimetry, and pattern electroretinography (PERG) amplitude. MATERIALS AND METHODS: Ninety eyes of 45 patients with a diagnosis of Stargardt disease stage 1 were prospectively recruited at the University of Bologna. Selected patients were treated with photo-biomodulation therapy for 1 year for 10 minutes a day, twice a day, and 5 days per week for 12 months. A light emitting diode (LED) of 10 Hz and wavelength 650 nm was used. BCVA and microperimetry were assessed before treatment and 1 year after photo-biomodulation, whereas PERG was assessed at baseline, 1, 3, 6, and 12 months after treatment. RESULTS: BCVA improved from 0.7 [interquartile range (IQR)=0.6-0.9)] to 0.4 (IQR=0.2-0.5)] after treatment (95% CI=-0.3, -0.35; p=<0.001) and PERG negative wave at 35 ms (N35)-positive wave at 50 ms (P50) amplitude improved from 0.9 (IQR=0.74-1.21) to 2.12 (95% CI=1.11, 1.28; p<0.001). MP-1 Microperimetry improved from 26.5% (IQR=16.75-40) of median preferred retinal loci (PRL) within an area of 2° of diameter to 38% (IQR=29-50.25; 95% CI=10.50, 14.50; p=<0.001); on the other hand, PRL within 4° of diameter raised from 72% (IQR=51.5-80) to 80% (IQR=76-87) after photo-biomodulation (95% CI=4.50, 7.50; p<0.001). Also, patients with an improvement of more than 1.205 PERG N35-P50 ratio amplitude at 3 months and more than 1.29 at 6 months tended to present an improvement of more than 0.2 logMar in BCVA at 12 months (p=0.28, AUC=0.630; p=0.30, AUC=0.636). CONCLUSION: BCVA, PERG, and MP-1 significantly improved 1 year after treatment. Also, improvement of PERG N35-P50 amplitude at 3 and 6 months was correlated to BCVA improvement at 1 year, suggesting that PERG could be useful in predicting visual outcome after photo-biomodulation.

Risk factors in central retinal vein occlusion: A multi-center case-control study conducted on the Italian population : Demographic, environmental, systemic, and ocular factors that increase the risk for major thrombotic events in the retinal venous system.

PURPOSE: To explore the risk factors for central retinal vein occlusion (CRVO) by comparing a large sample of patients with healthy controls. MATERIALS AND METHODS: Multi-center case-control study. The study group includes patients affected by central retinal vein occlusion, confirmed angiographically, aged 50 years old or above (Group A). The control group includes healthy subjects without an history of retinal vein occlusion (Group B). Outcome measures: age, gender, active smoking, presence of uncontrolled arterial hypertension (uHTN), presence of the following comorbidities: diabetes mellitus type II (DMII), chronic liver disease (CLD), chronic kidney disease (CKD), thyroid disease (TD), systemic lupus erythematosus (SLE), hyperhomocystenemia (HHcy), dyslipidemia (DLip), carotid artery disease (CAD), glaucoma, atrial fibrillation (AF), migraine headache (MH), chronic obstructive pulmonary disease (COPD), obstructive sleep apnea syndrome (OSAS), history of myocardial infarction (MI). Odds-ratios were calculated with logistic regression analysis. RESULTS: A total of 203 patients (Group A) and 339 controls (Group B). Statistically-significant differences were found for the following variables: age (OR: 1.109 [1.081-1.138], p < .001), active smoking (OR: 2.048 [1.210- 3.466], p < .008), DMII (OR: 4.533 [2.097-9.803], p < .001), HHcy (OR: 4.507 [2.477-10.001 ], p < .001), DLip (OR: 2.255 [1.352-3.762], p = .002), CAD (OR: 6.632 [2.944- 14.942], p < .001), glaucoma (OR: 4.656 [2.031-10.673], < .001), OSAS (OR: 1.744 [1.023-2.975], < .041), uHTN (OR: 3.656 [2.247-5.949], < .001). No statistically-significant differences were found for the other variables. CONCLUSIONS: Older age, active smoking, as well as presence of DMII, HHcy, DLip, CAD, glaucoma, OSAS, and uHTN, all increase the risk for CRVO. A comprehensive assessment of patients with CRVO is paramount. Adequate control of all the aforementioned risk factors is likely of great significance in reducing the incidence of CRVO among the general population, and it likely plays an important role in improving the prognosis following the occlusive event.

Utility of Ocular Motility Tests in Orbital Floor Fractures with Muscle Entrapment That is Not Detected on Computed Tomography.

PURPOSE: Determine the usefulness of ocular motility testing to detect the presence of muscle entrapment. MATERIALS AND METHODS: Cross-sectional study of patients with symptoms of diplopia secondary to facial trauma. Inclusion criteria: age between 20 and 80 years; symptoms of diplopia following facial trauma; presence of orbital floor fracture confirmed radiologically; presence of muscle entrapment confirmed at the time of surgery; best-corrected visual acuity of 0.6 or more. Exclusion criteria: muscle entrapment visible on computed tomography; candidate for immediate surgical correction; prior history of strabismus surgery. Outcome measures: Abnormal Head Position (AHP), Hirschberg Corneal Reflexes (CR), Cover/Uncover and Alternating Cover Test, Hertel exophthalmometry, Near Point of Convergence (NPC), Kestenbaum Limbus test, Red Filter test, and Hess screen test. RESULTS: Forty-six subjects (38 males, 8 females, mean age 27 ± 3.3 SD years). Pre-operative assessment: forty-six (100%) reported diplopia on the Red Filter test and showed some degree of abnormality on the Hess Screen test. Forty-two (91%) showed AHP. Forty-one (89%) had exophthalmometry values that differed 2 mm or more between the two eyes and insufficient NPC. Thirty-two (69.6%) showed deficits of 3 mm or more on the Kestenbaum Limbus test. Sixteen (35%) had abnormal Hirschberg corneal reflexes. Eleven (24%) demonstrated constant or intermittent strabismus. CONCLUSION: Ocular motility testing can differentiate non-invasively, pre-operatively, and cost-effectively the presence of muscle entrapment even when this is not visible on computed tomography.

Efficacy and safety of intravitreal Fluocinolone Acetonide microimplant (ILUVIEN®) in patients with chronic diabetic macular edema: 1 year follow-up.

PURPOSE: Evaluate the efficacy and safety of intravitreal 0.19 mg fluocinolone acetonide (FAc) micro implant in patients with chronic diabetic macular edema (cDME). METHODS: Prospective study recruiting subjects with cDME. Inclusion criteria: cDME for at least 2 years documented with OCT imaging; pseudophakia; previous treatments with laser photocoagulation and intravitreal injections of anti-VEGF and/or dexamethasone. Exclusion criteria: phakia; ocular hypertension; tractional component visible on OCT; glaucoma; previous vitrectomy. Outcome measures included best-corrected visual acuity (BVCA), intraocular pressure (IOP), and central macular thickness (CMT), measured 1, 3, 6, and 12 months post-injection. Data were compared with the Friedman test and significance was set at p < 0.05. RESULTS: A total of 18 eyes with a median duration of cDME of 45 months (25-118 months). The 77% of subjects either maintained or improved their BVCA. About 17% and 33% of subjects showed an improvement of 15 ETDRS letters or more at 3 and 12 months respectively. The 17% and 28% of subjects showed a CMT <250 microns at 3 and 12 months, respectively. The median change in CMT thickness was of -370 and -373.5 microns at 3 and 12 months post-injection respectively (p-value is 0.025). Changes in median IOP at 3 and 12 months post-injection were not statistically significant (p-value is 0.210). Ocular hypertension (OHT) was detected in two eyes (11%). CONCLUSION: The FAc micro implant has proved efficacy in improving and/or maintaining BVCA in 77% of patients with cDME up to 12 months post-injection. Ocular hypertension is the most common side effect but responds well to topical therapy.

Prolonged face mask use might worsen dry eye symptoms.

Purpose: The aim of this study was to explore whether prolonged and consistent face mask use might be associated with worsening of dry eye symptoms in patients with dry eye disease (DED). Methods: Subjects with a previous diagnosis of DED. Their OSDI scores were compared with those recorded in Fall 2019 using the Wilcoxon paired test. Participants were stratified by face mask use: heavy (Group A) or standard (Group B) face mask users. Heavy use was defined as wearing any type of face mask for at least 6 hours a day, at least 5 days per week in the last 2 months. Results: 67 subjects (mean age: 45.27 ± 10.06 SD years, 40% males and 60% females). Median OSDI score in Fall 2019: 18.75. Median OSDI in Spring 2020: 20.83. The Hodges-Lehmann median difference was 2.09 (95% CI [1.05, 4.17]) (P < 0.0001). The population was then stratified into heavy and standard face mask users: Group A included heavy users (31 subjects; mean age: 42.81 ± 10.48 SD years; 35% males and 65% females), Group B included standard users (36 subjects; mean age: 47.39 ± 9.31 SD years; 44% males and 56% females). The Hodges-Lehmann median difference was 5.21 (95% CI [3.13, 7.29]) in Group A (P < 0.0001), and 1.04 (95% [0],[ 2.08]) in Group B (P = 0.0177). Conclusion: Prolonged and consistent face mask use is associated with an increase in OSDI scores. Whether face mask use is responsible for the worsening of symptoms of DED remains to be elucidated.

Cancer Diagnostic Delay in Northern and Central Italy During the 2020 Lockdown Due to the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: We performed data collection concerning the coronavirus disease 2019 (COVID-19) pandemic-related delay in the diagnosis of cancers to individuate proper corrective procedures. METHODS: A comparison was made among the number of first pathologic diagnoses of malignancy made from weeks 11 to 20 of 2018, 2019, and 2020 at seven anatomic pathology units serving secondary care hospitals in northern-central Italy. RESULTS: Cancer diagnoses fell in 2020 by 44.9% compared with the average number recorded in 2018 and 2019. Melanoma and nonmelanoma skin cancer represented 56.7% of all missing diagnoses. The diagnostic decrease in colorectal (-46.6%), prostate (-45%), and bladder (-43.6%) cancer was the most relevant among internal malignancies; for prostate, however, high-grade tumors were only moderately affected (-21.7%). CONCLUSIONS: Diagnosis of cutaneous malignancies was mostly affected by the lockdown; among internal malignancies, corrective actions were mostly needed for colorectal cancer and invasive bladder cancer.

Effects of Repeated Intravitreal Injections of Dexamethasone Implants on Intraocular Pressure: A 4-Year Study.

PURPOSE: Dexamethasone and other corticosteroids are administered intravitreally to treat a variety of retinal diseases. As a side effect, they can alter intraocular pressure (IOP). The purpose of this study is to describe the incidence, severity, and management of ocular hypertension following the administration of multiple intravitreal injections of dexamethasone implants. MATERIALS AND METHODS: A total of 78 eyes of 78 subjects (males 62%; females 38%; mean age 67 ± 13 years SD) received a total of 152 intravitreal injections of 0.7 mg dexamethasone implants over 4 years. Indications included retinal vein occlusion (87%), diabetic macular edema (9%), wet-type age-related macular degeneration (4%). Ocular hypertension was defined as intraocular pressure above 23 mmHg or any pressure increase of 10 mmHg or more from baseline values. IOP was measured by applanation tonometry before the injection (T0), as well as one week (T1), one month (T2), and three months (T3) afterwards. RESULTS: Five percent (4/78) of subjects developed ocular hypertension after the 1st injection. On the second and third rounds, additional 7.2% (3/42) and 4.2% (1/24) of subjects developed the same side effect. Among the 8 subjects who received a fourth injection, none was found with OHT. Pressure elevations were detected at T2 and T3. In all patients, topical medical therapy was sufficient to lower the IOP below threshold. Mean pressure variations following the first injection as compared to previous recorded values were +0.97 mmHg (T1), +0.92 mmHg (T2), and -0.41 mmHg (T3) (p < 0.05). Mean pressure variations following the second injection were +0.54 mmHg (T1), +0.23 mmHg (T2) and -0.66 mmHg (T3) (p < 0.05). CONCLUSION: Ocular hypertension is a recognized side effect of intravitreal dexamethasone. Some patients develop it right after the first injection, while others develop it subsequently, on the 2nd or 3rd round. This side effect becomes most apparent 30-90 days following the implantation procedure and responds well to topical pressure-lowering medications.

Inherited and acquired thrombophilia in adults with retinal vascular occlusion: A systematic review and meta-analysis.

BACKGROUND: Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear. OBJECTIVES: This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature. PATIENTS/METHODS: PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated. RESULTS: Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in <2%. The MTHFR C677T and PAI 4G homozygous polymorphism were observed in 13% (95% CI: 10-17) and 23% (95% CI: 16-31) of RVO, respectively; 8% presented APL antibodies. Similar findings were observed in individuals with RAO. CONCLUSIONS: Compared with healthy subjects, patients with retinal vascular occlusion showed similar prevalences of inherited and acquired thrombophilias. These findings do not support routine thrombophilia screening in individuals with RAO or RVO.

Involvement of the biogenic active amine agmatine in mitochondrial membrane permeabilization and release of pro-apoptotic factors.

Agmatine (AGM) produces a dual effect on the mitochondrial permeability transition (MPT) mechanism in rat liver mitochondria: at low concentrations, it induces the phenomenon, at high ones, inhibits it. The prevention at high concentrations is evidenced by the significant inhibition of mitochondrial swelling induced by Ca2+ and phosphate; in this condition, AGM both prevents the release of Apoptosis Inducing Factor (AIF) and enhances the release of other pro-apoptotic factors, such as cytochrome c (cyt c) and Smac/DIABLO. As these factors are released without MPT induction, the involvement of mitochondrial outer membrane permeabilization (MOMP) could be hypothesized. Cyclosporin A (CsA), a powerful inhibitor of MPT, enhanced the AGM-mediated inhibition of swelling, and surprisingly, prevented the release of cyt c and Smac/DIABLO. In the presence of Ca2+, AGM also activated the Bcl-2 family protein Bax, a key factor in inducing MOMP, which is inactivated by CsA. Together with the voltage-dependent anion channel (VDAC), Bax forms channels in the outer membrane further supporting the involvement of MOMP in the release of pro-apoptotic factors. In view of the fact that VDAC was inactivated by ruthenium red, which in turn inhibited the release of cyt c, it can be hypothesized that, on the one hand, AGM inhibits MPT induction and, on the other, it selectively permeabilizes the outer membrane via MOMP induction.