[Show abstract][Hide abstract] ABSTRACT: Purpose
. An expanded access program (PRIDE study) in Italy to provide ranibizumab 0.5 mg to diabetic macular edema (DME) patients, prior to reimbursement.
. Open-label, prospective, phase IIIb study. Majority of patients were not treatment-naïve before enrollment. Patients received ranibizumab as per the EU label (2011). Safety was assessed by incidences of ocular/systemic adverse events (AEs) and serious AEs (SAEs) and efficacy in terms of visual acuity (VA) change from baseline (decimal score or Snellen (20/value)).
. Overall, 515 patients (83.5%) completed the study. In unilateral/bilateral patients, commonly observed AEs were cardiac disorders (1.3%/1.3%) and nervous system disorders (1.3%/1.1%); SAEs were reported in 4.5%/4.8% of patients. Acute renal failure, lung carcinoma, and cardiac arrest were the causes of death in one unilateral and two bilateral patients. Ranibizumab improved/maintained VA (Snellen (20/value)/decimal scores) in both unilateral (up to −16.7/1.5) and bilateral patients (up to −23.6/1.2) at Month 5, with a mean of 4.15 and 4.40 injections, respectively. Overall, no difference was observed in the VA outcomes and treatment exposure between unilateral/bilateral patients.
. The PRIDE study provided early ranibizumab access to >600 Italian patients. Ranibizumab was well-tolerated and improved/maintained VA in 40.2%–68.8% patients, with no differences in case of unilateral or bilateral pathology. The study is registered with EudraCT.
Journal of Ophthalmology 08/2015; 2015:324841. DOI:10.1155/2015/324841 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PurposeDiabetic macular oedema (DMO) is a leading cause of blindness in working-age adults. Slow-release, nonbioerodible fluocinolone acetonide (FAc) implants have shown efficacy in the treatment of DMO; however, the National Institute for Health and Care Excellence recommends that FAc should be used in patients with chronic DMO considered insufficiently responsive to other available therapies only if the eye to be treated is pseudophakic. The goal of this analysis was to examine treatment outcomes in phakic patients who received 0.2 μg/day FAc implant.Methods
This analysis of the phase 3 FAME (Fluocinolone Acetonide in Diabetic Macular Edema) data examines the safety and efficacy of FAc implants in patients who underwent cataract extraction before (cataract before implant (CBI) group) or after (cataract after implant (CAI) group) receiving the implant. The data were further examined by DMO duration.ResultsBest corrected visual acuity (BCVA) after 36 months was comparable in the CAI and CBI groups. Both the percentage of patients gaining ≥3 lines of vision and mean change in BCVA letter score were numerically greater in the CAI group. In addition, most patients who underwent cataract surgery experienced a net gain in BCVA from presurgery baseline as well as from original study baseline.Conclusions
These data support the use of 0.2 μg/day FAc implants in phakic as well as in pseudophakic patients. These findings will serve as a pilot for design of future studies to evaluate the potential protective effect of FAc implants before cataract surgery in patients with DMO and cataract.Eye advance online publication, 26 June 2015; doi:10.1038/eye.2015.98.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To report long-term results of photodynamic therapy (PDT) in young patients affected by Best vitelliform macular dystrophy (VMD) complicated by choroidal neovascularization (CNV).
We evaluated a group of 30 VMD patients with confirmed mutations in the BEST1 gene. Five of these patients had been diagnosed with CNV when younger than 15 years of age and three of them were treated by PDT. After the treatment they were followed for an average period of 77 months (range 62-99).
In all the treated eyes visual acuity was stable during the first year of follow-up and then slowly improved even some years after the treatment. The improvement in visual acuity was associated with the development of fibrous tissue in the macula.
PDT was a safe procedure in our series of pediatric patients with VMD complicated by CNV. It was followed by a CNV regression and a consequent improvement in visual acuity which continued to progress even several years after the treatment.
[Show abstract][Hide abstract] ABSTRACT: To analyze the spectrum of sequence variants in the MYO7A and USH2A genes in a group of Italian patients affected by Usher syndrome (USH).
Thirty-six Italian patients with a diagnosis of USH were recruited. They received a standard ophthalmologic examination, visual field testing, optical coherence tomography (OCT) scan, and electrophysiological tests. Fluorescein angiography and fundus autofluorescence imaging were performed in selected cases. All the patients underwent an audiologic examination for the 0.25-8,000 Hz frequencies. Vestibular function was evaluated with specific tests. DNA samples were analyzed for sequence variants of the MYO7A gene (for USH1) and the USH2A gene (for USH2) with direct sequencing techniques. A few patients were analyzed for both genes.
In the MYO7A gene, ten missense variants were found; three patients were compound heterozygous, and two were homozygous. Thirty-four USH2A gene variants were detected, including eight missense variants, nine nonsense variants, six splicing variants, and 11 duplications/deletions; 19 patients were compound heterozygous, and three were homozygous. Four MYO7A and 17 USH2A variants have already been described in the literature. Among the novel mutations there are four USH2A large deletions, detected with multiplex ligation dependent probe amplification (MLPA) technology. Two potentially pathogenic variants were found in 27 patients (75%). Affected patients showed variable clinical pictures without a clear genotype-phenotype correlation.
Ten variants in the MYO7A gene and 34 variants in the USH2A gene were detected in Italian patients with USH at a high detection rate. A selective analysis of these genes may be valuable for molecular analysis, combining diagnostic efficiency with little time wastage and less resource consumption.
[Show abstract][Hide abstract] ABSTRACT: Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.
Journal of Ophthalmology 11/2014; DOI:10.1155/2014/281010 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To evaluate the refractive outcomes and rotational stability of a 4-haptic toric intraocular lens (IOL) in myopic eyes and the correlations between IOL rotation and refractive sphere, axial length (AL), and white-to-white (WTW) diameter. SETTING: Eye Clinic, Careggi Hospital, Florence, Italy. DESIGN: Prospective case series. METHODS: Phacoemulsification cataract extraction and implantation of an AT Torbi 709M IOL were performed. Corneal astigmatism was 1.50 diopters (D) or greater and the AL between 25.0 mm and 27.0 mm in all eyes. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, and IOL axis were evaluated preoperatively and postoperatively up to 6 months. RESULTS: The study enrolled 20 eyes (20 patients). The UDVA and CDVA improved significantly postoperatively (P<.001). The mean refractive spherical equivalent decreased significantly from -7.10 D +/- 1.78 (SD) preoperatively to -0.55 +/- 0.25 D 1 day postoperatively (P<.001) and remained stable thereafter. Vector analysis showed that 90% and 85% of the eyes were within +/-0.25 D for J0 and J45, respectively. At 3 months and 6 months, the mean IOL rotation was 2.66 +/- 1.53 degrees and 3.00 +/- 1.69 degrees, respectively (P<.001), with 95% of eyes and 90% of eyes, respectively, within +/-5 degrees. A positive correlation was found between IOL rotation and preoperative sphere; none was found with AL and WTW. CONCLUSIONS: Implantation of the 4-haptic toric IOL in myopic eyes was effective and safe. The IOL showed no significant rotation over the 6-month follow-up. (C) 2014 ASCRS and ESCRS
Journal of Cataract and Refractive Surgery 09/2014; 40(9):1479-87. DOI:10.1016/j.jcrs.2013.12.024 · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy of intravitreal ranibizumab with a "pro re nata" regimen in the treatment of nonsubfoveal neovascular membranes secondary to age-related macular degeneration.
Retrospective noncomparative case series. Thirty-one eyes with naive nonsubfoveal neovascularization secondary to age-related macular degeneration were consecutively enrolled and treated with ranibizumab intravitreal injections according to a pro re nata regimen. The follow-up was performed monthly up to 6 months and quarterly up to 2 years (25 patients). Early treatment diabetic retinopathy study best-corrected visual acuity and lesion size analysis with fluorescein angiography were recorded.
The mean baseline early treatment diabetic retinopathy study best-corrected visual acuity worsened from 20/40 (0.28 logMAR) at baseline to 20/50 (0.42 logMAR) at 1-year follow-up and 20/60 (0.53 logMAR) at 2-year follow-up. The mean lesions size nearly doubled from baseline at the 2-year follow up (1.19-2.47 mm). Twenty-two patients had one or more recurrences at 1-year follow-up. All 25 patients developed a recurrence at 2 years with 7 cases developing a recurrence by 12 months. Twelve cases progressed to subfoveal lesions by the 24-month visit.
Other regimens described in the literature might result in a more the satisfactory outcome using more frequent follow-up and more frequent intravitreal injections.
[Show abstract][Hide abstract] ABSTRACT: An impairment of ocular blood flow regulation is commonly considered one of the main pathogenetic mechanisms involved in the development of several eye diseases, like glaucoma. The aim of this study was to investigate whether an alteration of ocular blood supply induced by peripheral vasoconstriction might be detected by measuring the ocular surface temperature. The ocular surface temperature was evaluated in a group of 38 healthy young subjects (28 males and 10 females; mean age: 25.4 ± 4.1 years) by infrared thermography. For each subject, the experimental procedure consisted of two thermographic acquisitions both lasting 10 s, recorded before and during the immersion of both hands in a mixture of ice and water (1.6 °C ± 0.4 °C). Specifically, the second acquisition began 20 s after the hand immersion. Analysis of variance was used to compare the ocular surface temperature of the two profiles. The analysis of infrared images was carried out every 2 s: at the eye opening (t0) until 10 s (t5), for both profiles. Data showed that ocular surface temperature increased significantly (p-value < 0.05), especially near the sources of ocular blood supply, that is, temporal and nasal areas (mean increasing temperature at t0 for P1 = 0.12 °C ± 0.13 °C). Therefore, these results suggest a response of the ocular hemodynamic to the peripheral vasoconstriction. The ocular surface temperature may represent a cheap, non-invasive and non-time-consuming test to evaluate ocular vaso-regulation.
[Show abstract][Hide abstract] ABSTRACT: Abstract Purpose: To investigate the safety of trypan blue, brilliant blue G (BBG), Evans blue (EB), patent blue, Chicago blue (CB), and bromophenol blue (BB), with and without halogen and xenon light exposure. Methods: All dyes were diluted in a balanced saline solution at a concentration of 0.5%. Cells of the human RPE line ARPE-19 and rat RGC5 were exposed to vital dyes for 5 min. Experiments with and without xenon or halogen illumination were performed. The viability of ARPE-19 and RGC5 cells was determined at 12, 24, or 120 h by a cell proliferation assay using WST-1 reagent. The apoptotic events as well as cell numbers were registered for 72 h and counted by time-lapse videomicroscopy. Results: There was no evidence of ARPE-19 or RGC5 toxicity, immediate (0 and 24 h) or delayed (120 h), following exclusive exposure to each single dye. After halogen light exposure, ARPE-19 cell lines did not show any significant toxicity, except for when they were exposed to EB. After xenon illumination, ARPE-19 cells showed a marked decrease in cell viability when exposed to EB or CB and a moderate decrease when exposed to BBG and BB. After xenon illumination, RGC5 cells showed the highest decrease in cell viability when exposed to EB and CB; BB caused the same decrease in cell viability as in ARPE-19 cells. Conclusion: Interaction of light from endo-illumination source and blue vital dyes may increase the risk of retinal toxicity.
Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2014; 30(5). DOI:10.1089/jop.2013.0213 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To compare the efficacy and safety of ranibizumab 0.5 mg, guided by visual acuity (VA) stabilization or disease activity criteria, versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV).
Phase III, 12-month, randomized, double-masked, multicenter, active-controlled study.
Patients (N = 277) with visual impairment due to myopic CNV.
Patients were randomized to receive ranibizumab on day 1, month 1, and thereafter as needed guided by VA stabilization criteria (group I, n = 106); ranibizumab on day 1 and thereafter as needed guided by disease activity criteria (group II, n = 116); or vPDT on day 1 and disease activity treated with ranibizumab or vPDT at investigators' discretion from month 3 (group III, n = 55).
Main Outcome Measures
Mean average best-corrected visual acuity (BCVA) change from baseline to month 1 through months 3 (primary) and 6, mean BCVA change and safety over 12 months.
Ranibizumab treatment in groups I and II was superior to vPDT based on mean average BCVA change from baseline to month 1 through month 3 (group I: +10.5, group II: +10.6 vs. group III: +2.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; both P < 0.0001). Ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month 1 through month 6 (group II: +11.7 vs. group I: +11.9 ETDRS letters; P < 0.00001). Mean BCVA change from baseline to month 12 was +13.8 (group I), +14.4 (group II), and +9.3 ETDRS letters (group III). At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab injections over 12 months. No deaths or cases of endophthalmitis and myocardial infarction occurred.
Ranibizumab treatment, irrespective of retreatment criteria, provided superior BCVA gains versus vPDT up to month 3. Ranibizumab treatment guided by disease activity criteria was noninferior to VA stabilization criteria up to month 6. Over 12 months, individualized ranibizumab treatment was effective in improving and sustaining BCVA and was generally well tolerated in patients with myopic CNV.
Proprietary or commercial disclosure may be found after the references.
[Show abstract][Hide abstract] ABSTRACT: Purpose: To assess the efficacy of intravitreal anti-vascular endothelial growth factor (VEGF) treatment of vascularized pigment epithelial detachment (PED) due to age-related macular degeneration (AMD).
Methods: A total of 26 patients with vascularized PED secondary to AMD were retrospectively analyzed and treated with anti-VEGF intravitreal injections according to a PRN regimen after 3 initial injections. Best-corrected visual acuity (BCVA), optical coherence tomography, and fluorescein angiography were performed at baseline and quarterly.
Results: Mean follow-up ranged from 9 to 26 months (mean 13.5). There was a deterioration in mean BCVA from 0.46 at baseline to 0.79 logMAR at 12 months (p<0.001). The mean PED greatest linear diameter (GLD) increased from 4499 at baseline to 5206 μm at 1-year follow-up (p<0.001). The mean PED maximum height decreased from 669 μm at baseline to 305 μm at 1-year follow-up (p = 0.001). The mean central retinal thickness (CRT) was unchanged (from 277 to 209 μm at 1 year follow-up) (p = 0.099). No effect was seen on the change of VA according to groups of baseline predictors as defined by the medial value: baseline VA, PED height, and CRT (p>0.10).There was a borderline trend (p = 0.064) that GLD affected response to treatment. The mean number of injections was 5.5 (3 to 9). Seven out of 26 (27%) patients developed a retinal pigment epithelium (RPE) tear.
Conclusions: Intravitreal anti-VEGF therapy, with a PRN regimen, did not prevent visual acuity loss or RPE tear.
European journal of ophthalmology 11/2013; 24(3). DOI:10.5301/ejo.5000388 · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the tolerability on healthy volunteers and the efficacy on subjects affected by chronic moderate/severe blepharitis of a 5% glycyrrhizin and copolymer poly(ethylene glycol)/poly(propylene glycol)(PEG/PPG) ophthalmic solution.
The study was a randomized, controlled, open label, intra-patient monocentric study. It consisted of two different phases, the assessment of tolerability phase on 20 healthy volunteers, and the evaluation of the efficacy on 21 subjects affected by chronic moderate/severe blepharitis; the treatment period was 2 weeks, followed by 1-week of follow-up. In the efficacy phase, in both eyes, eyelid hygiene was also performed. At day 0, 3, 7, 14, and 21 a complete ophthalmological examination was performed. In the tolerability phase, signs of clinical toxicity were recorded and subject-reported symptoms were collected using a questionnaire. In the efficacy phase, global signs and symptoms of blepharitis scores were collected using standardized photographic scales and questionnaire. The statistical analysis was performed using the Wilcoxon signed-rank test.
No ocular signs of drug toxicity were reported. During the treatment period for tolerability phase, there were statistically significant higher scores of tearing and ocular discomfort in the tolerability study group versus the tolerability control group. In the efficacy phase, differences between global scores of the two groups were statistically significant at day 0 (score of the efficacy study group was higher than the efficacy control group; P = 0.005) and at day 21 (score of the efficacy study group was lower than the efficacy control group (P ≤ 0.001).The difference of global scores at day 3, 7, 14, and 21 versus day 0 was statistically significant in both groups. No serious adverse events occurred.
The 5% glycyrrhizin ophthalmic solution was well tolerated in healthy volunteers and in patients with chronic moderate/severe blepharitis, and in association with eyelid hygiene showed good clinical anti-inflammatory activity that lasted after instillation suspension.
[Show abstract][Hide abstract] ABSTRACT: Background:
Endophthalmitis is a rare but severe complication of vitrectomy.
Post-surgical endophthalmitis is suspected to be more frequent after microincisional (23- and 25-gauge) compared with standard (20-gauge) vitrectomy.
We conducted a systematic review of studies that compared microincisional and standard vitrectomy by searching MEDLINE and EMBASE up to November 2012. We used the Bayesian meta-analysis method to compute the odds ratio (OR) of endophthalmitis. We conducted subgroup analyses to compare the effect of different incision types and use of perioperative antibiotics.
We identified 3 small randomized and 18 nonrandomized studies that reported 68 cases of endophthalmitis in 148 643 participants. The overall OR of endophthalmitis for microincisional versus standard vitrectomy was 2.3 (95% credible interval [CrI], 0.8-5.8). We found an increased risk of endophthalmitis using a microincisional straight approach compared with standard vitrectomy (OR, 15.1; 95% CrI, 2.01-179), but not for a beveled approach (OR, 0.82; 95% CrI, 0.23-2.28). The OR of studies that reported on mixed microincision was between these 2 values (OR, 4.4; 95% CrI, 1.32-14.3). We estimated that the overall rate of endophthalmitis with 20-gauge vitrectomy was 3 cases in 10 000 procedures, and the probability that a beveled microincision increases the rate of endophthalmitis to more than 6 or 9 events was small (no more than 5% or 1%, respectively).
We did not find an increased risk of endophthalmitis for microincisional vitrectomy compared with standard vitrectomy. The beveled approach seems to be safer than a straight approach, supporting the current recommendation of its adoption in microincisional vitrectomy. However, these findings must be interpreted cautiously because of the small number of endophthalmitis events reported from included studies.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To investigate the simultaneous association of several psychophysical measures with reading ability in patients with mild and moderate low vision attending rehabilitation services.
Standard measurements of reading ability (Minnesota Reading [MNREAD] charts), visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] charts), contrast sensitivity (Pelli-Robson charts), reading contrast threshold (Reading Explorer [REX] charts), retinal sensitivity, and fixation stability and localization (Micro Perimeter 1 [MP1] fundus perimetry) were obtained in 160 low vision patients with better eye visual acuity ranging from 0.3 to 1.0 logarithm of the minimum angle of resolution and affected by either age-related macular degeneration or diabetic retinopathy.
All variables were moderately associated with reading performance measures (MNREAD reading speed and reading acuity and REX reading contrast threshold), as well as among each other. In a structural equation model, REX reading contrast threshold was highly associated with MNREAD reading speed (standardized coefficient, 0.63) and moderately associated with reading acuity (standardized coefficient, -0.30). REX test also mediated the effects of Pelli-Robson contrast sensitivity (standardized coefficient, 0.44), MP1 fixation eccentricity (standardized coefficient, -0.19), and the mean retinal sensitivity (standardized coefficient, 0.23) on reading performance. The MP1 fixation stability was associated with both MNREAD reading acuity (standardized coefficient, -0.24) and MNREAD reading speed (standardized coefficient, 0.23), while ETDRS visual acuity only affected reading acuity (standardized coefficient, 0.44).
Fixation instability and contrast sensitivity loss are key factors limiting reading performance of patients with mild or moderate low vision. REX charts directly assess the impact of text contrast on letter recognition and text navigation and may be a useful aid in reading rehabilitation.
[Show abstract][Hide abstract] ABSTRACT: To compare the cytotoxic effects of preservative-free azithromycin on corneal epithelial cells in vivo with those of preservative-free netilmicin and levofloxacin, and the preservative benzalkonium chloride (BAK).
Rabbit corneal epithelial cells in vitro were incubated for 15 minutes or 6 hours with commercially available ophthalmic preservative-free netilmicin 0.3%, levofloxacin 0.3%, or azithromycin 1.5% preparations or different concentrations of unpreserved azithromycin and different concentrations of BAK. Qualitative analysis was undertaken using phase-contrast optics to examine the morphological aspects of cell cultures and quantitative analysis was undertaken by measuring the release of the cytoplasmic enzyme lactate dehydrogenase into the medium immediately and 24 hours after exposure to drugs. Finally, we observed the wound-healing rate of mechanically injured corneal epithelial cells exposed to each antibiotic ophthalmic preparation for 48 hours.
Our results show that both the commercially available unpreserved mono-dose preparation of azithromycin and ophthalmic preparations of azithromycin up to a concentration of 1.5% were virtually devoid of harmful effects under our experimental conditions. This was not significantly different from the results obtained for the other antibiotic preparations (P > 0.05) tested, but was unlike the results obtained for BAK. Azithromycin 1.5% also showed good recovery properties after a mechanical wound test.
Under our experimental conditions, unpreserved azithromycin 1.5% showed a much lower toxicity than BAK and did not interfere with the wound-healing process.
[Show abstract][Hide abstract] ABSTRACT: P urpose : To evaluate the natural history of a case of retinoschisis with giant outer layer break and retinal detachment.
M ethods : A 42-year-old patient with a sudden paracentral scotoma in the visual field of the right eye underwent the following examinations: best-corrected visual acuity, slit-lamp biomicroscopy, optical coherence tomography, ocular echography, and fundus photography .
R esults : The eye examination revealed inferotemporal retinoschisis-detachment with a giant outer retinal layer break and absence of foveal involvement. No breaks in the internal retinal layer were noted. No treatment was advised in the right eye. During the 3-year follow-up, a progressive reabsorption of subretinal fluid was detected and visual acuity remained unchanged.
C onclusions : Deliberate nontreatment of a case of nonprogressive retinoschisis-detachment carries less risk of serious complications or loss of vision than does either surgical or prophylactic treatment.
European journal of ophthalmology 05/2013; 23(5). DOI:10.5301/ejo.5000310 · 1.07 Impact Factor