Teresio Avitabile

Standard-Fluence versus Low-Fluence Photodynamic Therapy in Chronic Central Serous Chorioretinopathy: A Nonrandomized Clinical Trial

PURPOSE To evaluate the efficacy of low-fluence compared with standard-fluence rate photodynamic therapy (PDT) for treating chronic central serous chorioretinopathy. DESIGN Prospective, multicenter, investigator-masked, nonrandomized clinical trial. METHODS Forty-two eyes (42 patients) with chronic central serous chorioretinopathy were enrolled; 19 eyes received indocyanine green angiography-guided standard-fluence PDT (50 J/cm(2)) and 23 eyes received indocyanine green angiography-guided low-fluence PDT (25 J/cm(2)). Primary outcome measures were the changes in mean logarithm of the minimal angle of resolution best-corrected visual acuity and the rate of eyes with complete subretinal fluid reabsorption. Secondary outcomes were the changes in central foveal thickness and choroidal perfusion. RESULTS Mean logarithm of the minimal angle of resolution best-corrected visual acuity improved significantly at all time points (P < .01), in the standard-fluence group from 0.43 to 0.24 at 12 months and in the low-fluence-group from 0.46 to 0.16, without significant difference between the 2 groups. At 12 months, a complete subretinal fluid reabsorption was seen in 15 standard-fluence-treated and 21 low-fluence-treated eyes (79% vs 91%; P = .5). In 1 standard-fluence eye, choroidal neovascularization developed at 3 months, and this eye received further PDT; in the other eyes, at 12 months, a moderate-significant choriocapillaris nonperfusion was seen in 8 standard-fluence-treated and 0 low-fluence-treated eyes (44% vs 0%; P = .002). CONCLUSIONS In most of the eyes, both standard-fluence PDT and low-fluence PDT resulted in complete subretinal fluid reabsorption with visual acuity improvement. Choroidal hypoperfusion related to PDT could be reduced by low-fluence PDT.

L -Carnitine Supplementation to Diet: A New Tool in Treatment of Nonalcoholic Steatohepatitis — A Randomized and Controlled Clinical Trial

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is a known metabolic disorder of the liver. No treatment has been conclusively shown to improve NASH or prevent disease progression. The function of L-carnitine to modulate lipid profile, glucose metabolism, oxidative stress, and inflammatory responses has been shown. The aim of this study was to evaluate the effects of L-carnitines supplementation on regression of NASH.METHODS:In patients with NASH and control subjects, we randomly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen. We evaluated liver enzymes, lipid profile, fasting plasma glucose, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment (HOMA)-IR, body mass index, and histological scores.RESULTS:At the end of the study, L-carnitine-treated patients showed significant improvements in the following parameters: aspartate aminotransferase (P=0.000), alanine aminotransferase (ALT) (P=0.000), γ-glutamyl-transpeptidase (γ-GT) (P=0.000), total cholesterol (P=0.000), low-density lipoprotein (LDL) (P=0.000), high-density lipoprotein (HDL) (P=0.000), triglycerides (P=0.000), glucose (P=0.000), HOMA-IR (P=0.000), CRP (P=0.000), TNF-α (P=0.000), and histological scores (P=0.000).CONCLUSIONS:L-carnitine supplementation to diet is useful for reducing TNF-α and CRP, and for improving liver function, glucose plasma level, lipid profile, HOMA-IR, and histological manifestations of NASH.

Enhanced Depth Imaging Optical Coherence Tomography of the Choroid in Idiopathic Macular Hole: A Cross-sectional Prospective Study

PURPOSE To determine the choroidal thickness in the macular area in patients with idiopathic macular hole in one eye and an unaffected fellow eye and in healthy controls. DESIGN Cross-sectional, prospective study. METHODS Twenty-two patients with a full-thickness unilateral idiopathic macular hole and 22 age- and sex-matched controls were recruited. Enhanced depth imaging optical coherence tomography images were obtained by using spectral-domain optical coherence tomography. The choroidal thickness was measured in the subfoveal area and 1000 μm and 2000 μm away from the fovea in the nasal and temporal regions. The diameter of the macular hole and the axial length were determined. RESULTS Choroidal thickness was significantly different across the 3 groups at all locations (P < .001, analysis of variance). The choroid was significantly thinner in eyes with idiopathic macular hole and in unaffected fellow eyes than in the control group (P < .01, Tukey-Kramer test). The mean subfoveal choroidal thickness was 183.2 μm in the idiopathic macular hole group, 196.6 μm in the fellow-eye group, and 245.0 μm in the control group. A negative correlation between subfoveal choroidal thickness and axial length was found in all groups (macular hole, r = -0.53, P = .01; fellow eyes, r = -0.56, P < .01; controls, r = -0.52, P = .01); in control eyes, a negative correlation was found between choroidal thickness and age (r = -0.48, P = .02). CONCLUSIONS Choroidal thickness was reduced in eyes with idiopathic macular hole and also in fellow unaffected eyes. This may suggest a contributing role of the choroid in the pathogenesis of idiopathic macular hole.

Evaluation of central and peripheral corneal thickness with ultrasound biomicroscopy in normal and keratoconic eyes.

PURPOSE Our study was designed to calculate central and peripheral corneal thickness in patients affected with early stages of keratoconus and in normal subjects using ultrasound biomicroscopy (UBM). To obtain an objective and reliable assessment of the corneal thinning in affected eyes, we developed a keratoconus index (KI) by means of the UBM measurements. METHODS By means of the commercial version of the ultrasound biomicroscope (system model 840; Zeiss-Humphrey Instruments, San Leandro, CA, USA) using a 50-MHz probe, we studied 30 normal and affected eyes. In keratoconic eyes, we measured the thinnest corneal thickness (TCT) at the apex of the conus and at four peripheral sites at a distance of 2.5 mm from the central site (peripheral corneal thickness: PCT). The same procedure was performed in the normal eyes. To obtain an objective and reliable assessment of the corneal thinning, we calculated the ratio between the mean PCT and the mean TCT (Keratoconus Index: KI = PCT/TCT), in keratoconic eyes. In normal eyes, the KI was calculated on the basis of the ratio between the mean PCT and the mean central corneal thickness (CCT). RESULTS In keratoconic eyes, the mean corneal thickness at the thinnest part of the conus was significantly different from the CCT in normal patients (Students t test, p < 0.001). The peripheral measurements were not significantly different from keratoconic and normal eyes. The mean KI was 1.482 (SD, 0.095) in the keratoconic eyes, whereas it was 1.189 (SD, 0.086) in the normal subjects. The statistical analysis of the KI calculated on the basis of the UBM measurements showed that the KI values are significantly different from healthy subjects and from keratoconic patients (Students t test, p < 0.001). CONCLUSIONS UBM can be considered a useful tool in the study of keratoconus. We believe that calculation of the KI by means of UBM gives the possibility of obtaining an objective assessment of corneal thinning. Therefore this parameter can be useful in the staging and in the follow-up of these patients.

l-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes

BACKGROUND Patients with type 2 diabetes are under high oxidative stress, and levels of hyperglycemia correlate strongly with levels of LDL oxidation. Carnitine favorably modulates oxidative stress. OBJECTIVE This objective of this study was to evaluate the efficacy of L-carnitine on the reduction of oxidized LDL cholesterol in patients with type 2 diabetes. DESIGN Eighty-one patients with diabetes were randomly assigned to 1 of 2 treatment groups for 3 mo. The 2 groups received either 2 g L-carnitine once daily (n = 41) or placebo (n = 40). The following variables were assessed at baseline, after washout, and at 1, 2, and 3 mo of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B-100, oxidized LDL cholesterol, thiobarbituric acid-reactive substances, and conjugated dienes. RESULTS At the end of the study period, the L-carnitine-treated patients showed significant improvements compared with the placebo group in the following markers: oxidized LDL levels decreased by 15.1 compared with 3.0 U/L (P < 0.001); LDL cholesterol decreased by 0.45 compared with 0.16 mmol/L (P < 0.05); triglycerides decreased by 1.02 compared with 0.09 mmol/L (P < 0.001); apolipoprotein A1 concentrations decreased by 0.12 compared with 0.03 mg/dL (P < 0.05); apolipoprotein B-100 concentrations decreased by 0.13 compared with 0.04 mg/dL (P < 0.05); thiobarbituric acid-reactive substance concentrations decreased by 1.92 compared with 0.05 (P < 0.001), and conjugated diene concentrations decreased by 0.72 compared with 0.11 in the placebo group (P < 0.001). CONCLUSION Our study indicates that oral administration of L-carnitine reduces oxidized LDL cholesterol levels in patients with type 2 diabetes.

Biocompatibility and biodegradation of intravitreal hyaluronan implants in rabbits

To study the biocompatibility and the biodegradation rate in vivo of new intravitreal implants made with three different hyaluronic acid esters: Hyaff7, Hyaff11 and Hyaff11p75 (100% ethyl ester, 100 and 75% benzyl esters, respectively), the plugs were implanted through a sclerotomy at 3.5 mm from the limbus of rabbit eyes. In order to evaluate the in vivo biodegradation the shaft diameter of the plugs was measured by ultrasound biomicroscopy. Slit lamp microscopy, ophthalmoscopy and ERG were performed periodically. The effects of the implants on ocular tissues were also evaluated histologically. All the plugs showed a good biocompatibilitv. Plugs of both the total esters, Hyaff7 and Hyaff11, were found to undergo a slow dissolution process for 60 and 150 days, respectively. The partial benzyl ester, Hyaff11p75, was completely reabsorbed after 15 days. Analysis of variance showed a high correlation between biodegradation rate and the time of resorption (F = 90.5; p < 0.001). The biodegradation rate of each implant is related to the chemical structure of the three types of Hyaff (F = 4.51; p = 0.005). The present data suggest that intravitreal implants based on hyaluronic acid esters represent useful biocompatible and biodegradable devices for a potential drug delivery system in the treatment of posterior segment ocular diseases.

Allergic conjunctivitis: a comprehensive review of the literature

Ocular allergy represents one of the most common conditions encountered by allergists and ophthalmologists. Allergic conjunctivitis is often underdiagnosed and consequently undertreated. Basic and clinical research has provided a better understanding of the cells, mediators, and immunologic events, which occur in ocular allergy. New pharmacological agents have improved the efficacy and safety of ocular allergy treatment. An understanding of the immunologic mechanisms, clinical features, differential diagnosis, and treatment of ocular allergy may be useful to all specialists who deal with these patients. The purpose of this review is to systematically review literature underlining all the forms classified as ocular allergy: seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratocongiuntivitis, contact allergy, and giant papillary conjunctivitis.

Low-fluence photodynamic therapy in longstanding chronic central serous chorioretinopathy with foveal and gravitational atrophy.

Purpose To describe anatomic and functional outcomes in two patients with long-standing severe chronic central serous chorioretinopathy (CSC) with foveal and gravitational atrophy treated with low-fluence photodynamic therapy (PDT). Methods Two patients with a history of over 10 years of chronic CSC and development of gravitational tracts, with best-corrected visual acuity <20/200, were treated with PDT guided by indocyanine green angiography (ICGA) with a fluence of 25 J/cm2 at an irradiance of 300 mW. Follow-up examinations 1 and 9 months after therapy included measurement of near and far best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography and ICGA, optical coherence tomography, and microperimetry. Results At 1 and 9 months after low-fluence PDT, complete resolution of subretinal, intraretinal, and under retinal pigment epithelium fluid was observed in both patients. Far and near visual acuity improved in both eyes. Improvement of sensitivity and fixation stability were demonstrated by microperimetry. No treatment-related side effects were seen. Conclusions ICGA-guided low-fluence PDT seems effective and safe for treating long-standing chronic CSC.

Transconjunctival sutureless 25-gauge versus 20-gauge standard vitrectomy: correlation between corneal topography and ultrasound biomicroscopy measurements of sclerotomy sites.

Purpose: To determine the correlation between corneal shape changes and ultrasound biomicroscopy (UBM) findings at the sclerotomy sites in conventional 20-gauge (G) pars plana vitrectomy (PPV) and 25-G transconjunctival sutureless vitrectomy (TSV) and to compare the effectiveness of the two surgical methods. Design: Prospective, comparative, observational case series. Methods: Sixty consecutive eyes (60 patients) undergoing primary 3-port PPV. Thirty eyes (30 patients, group 20-G) were treated with 20-G standard PPV and 30 eyes (30 patients, group 25-G) with 25-G TSV. We compared healing of the sclerotomy sites in the two groups. We determined the correlation between corneal shape changes (surgically induced astigmatism) measured by videokeratography and the durations of scleral healing cicatrization by UBM within each group. Results: UBM examination showed that the 20-G sclerotomy sites took about 8 weeks to heal, measured as complete opposition, whereas healing of the 25-G TSV sclerotomy was quite rapid, with complete scleral opposition in about 4 weeks. Corneal topography analysis showed, during the early postoperative period, a surgically induced steepening of the cornea in both groups (20 G, 3.08 ± 0.56 diopters and 25 G, 0.805 ± 0.61 diopters, P < 0.001, Mann-Whitney test), which then decreased gradually, recovering to the preoperative level within two months in group 20 G (P > 0.05) and 1 month in group 25 G (P > 0.05). We found a strong statistical correlation between the mean surgically induced keratometric astigmatism and the mean UBM measures of scleral healing (r = 0.99 for group 20 G and r = 0.97 for group 25 G). Conclusion: After PPV, astigmatic changes are especially significant in the early postoperative period in 20-G group; the 25-G TSV system results in faster reduction of surgically induced keratometric astigmatism because of rapid cicatrization of the sclerotomy sites.

miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: Pathological and diagnostic implications.

Uveal melanoma (UM) represents approximately 5–6% of all melanoma diagnoses and up to 50% of patients succumb to their disease. Although several methods are available, accurate diagnosis is not always easily feasible because of potential accidents (e.g., intraocular hemorrhage). Based on the assumption that the profile of circulating miRNAs is often altered in human cancers, we verified whether UM patients showed different vitreous humor (VH) or serum miRNA profiles with respect to healthy controls. By using TaqMan Low Density Arrays, we analyzed 754 miRNAs from VH, vitreal exosomes, and serum of 6 UM patients and 6 healthy donors: our data demonstrated that the UM VH profile was unique and only partially overlapping with that from serum of the same patients. Whereas, 90% of miRNAs were shared between VH and vitreal exosomes, and their alterations in UM were statistically overlapped with those of VH and vitreal exosomes, suggesting that VH alterations could result from exosomal dysregulation. We report 32 miRNAs differentially expressed in UM patients in at least 2 different types of samples analyzed. We validated these data on an independent cohort of 12 UM patients. Most alterations were common to VH and vitreal exosomes (e.g., upregulation of miR-21,-34 a,-146a). Interestingly, miR-146a was upregulated in the serum of UM patients, as well as in serum exosomes. Upregulation of miR-21 and miR-146a was also detected in formalin-fixed, paraffin-embedded UM, suggesting that VH or serum alterations in UM could be the consequence of disregulation arising from tumoral cells. Our findings suggest the possibility to detect in VH and serum of UM patients “diagnostic” miRNAs released by the affected eye: based on this, miR-146a could be considered a potential circulating marker of UM.