Alfredo Reibaldi

Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study

PURPOSE To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). DESIGN Randomized, double-masked, phase 3 study. METHODS A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. RESULTS The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). CONCLUSIONS The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.

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.

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.

NINE-YEAR FOLLOW-UP OF TRABECULECTOMY WITH OR WITHOUT LOW-DOSAGE MITOMYCIN-C IN PRIMARY OPEN ANGLE GLAUCOMA

Aim: To evaluate the long-term efficacy and safety of trabeculectomy with or without low-dosage Mitomycin-C (MMC) in primary open-angle glaucoma (POAG). Methods: 114 patients affected by POAG, participating in a randomised clinical trial from 1995 to 1998, were re-examined and their chart reviewed. Patients had undergone in one eye a trabeculectomy with intraoperative application (2 min) of MMC (0.2 mg/ml) or balanced saline solution (BSS), and, if indicated, postoperative laser suture lysis, bleb needling and/or digital massage. Intraocular pressure (IOP), medical therapy, visual field, further glaucoma surgery, cataract surgery and complication rate (leakage, cataract progression, hypotony, blebitis, endophthalmitis) were evaluated. Results: 67 eyes had received MMC and 47 BSS. MMC-treated eyes had a lower mean IOP (13.33±3.35 vs 14.72±2.19 mm Hg, p = 0.014); in this group, an higher percentage of eyes had IOP⩽18 mm Hg (73.1% vs 51.1%, p = 0.027) and IOP⩽14 mm Hg (56.7% vs 31.9%, p = 0.015); a lower rate had further glaucoma surgery (9% vs 25.5%, p = 0.040), and visual-field damage progression (21.1% vs 48.6%, p = 0.009). No difference was seen in the complication rate: one MMC-treated eye developed blebitis. Conclusions: In POAG low-dose MMC with intensified postoperative management improved the outcome of the trabeculectomy with a low incidence of complications.

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.

Prospective, Multicenter Demographic and Epidemiological Study on Vernal Keratoconjunctivitis: A Glimpse of Ocular Surface in Italian Population

Purpose: To evaluate the frequency and epidemiological features of vernal keratoconjunctivitis (VKC) in Italy. Methods: a specific electronic clinical chart for vernal keratoconjunctivitis was created to standardize: 1) medical history; 2) diagnostic criteria; 3) signs and symptoms; and 4) treatments. This study involved 6 Italian referral centers for ocular surface diseases: between March 2005 and March 2006, all referred patients were included, clinical data collected and statistically examined. Results: The mean age of the vernal keratoconjunctivitis population (n = 156) was 13.8 ± 8.8 with 64.1% of subjects under 14 years of age and a male/female ratio of 3.5:1. Among VKC patients, 48.7% showed associated systemic allergic diseases. Only 32.1% of patients were positive for RAST and/or prick test. The limbal form (53.8%) was the most frequent subtype of vernal keratoconjunctivitis. Approximately 9% of patients showed a severe form of vernal keratoconjunctivitis. At the first visit patients were treated with: multiple action or mast cell stabilizer eye drops (58.1% and 41.3% of cases, respectively), topical corticosteroids alone (0.6%) or in association (26.8% of cases). All patients used topical steroids at least once in the studied year. Systemic antihistamine therapy was used by 25.6% of patients. In this cohort, 32.7% of patients required two or more examinations per year for exacerbations of their symptoms. Conclusion: Vernal keratoconjunctivitis is a severe ocular condition that mainly affects young males. Vernal keratoconjunctivitis is characterized by different clinical features and therapeutic responses, suggesting the need for a standardized therapeutic approach on the basis of a grading of disease severity.

Retinal detachment after silicone oil removal is prevented by 360° laser treatment

Aim: To investigate the effect of 360° laser retinopexy on the incidence of retinal detachment (RD) after silicone oil removal. Methods: In a prospective, randomised clinical trial, 303 patients (303 eyes) affected with primary (n = 211) or recurring (n = 92) rhegmatogenous RD treated by vitrectomy with silicone oil (1000 cSt) and endolaser photocoagulation of retinal breaks were randomised to receive 360° laser retinopexy or not. After at least 4 months, in eyes with a fully attached retina, the silicone oil was removed. The incidence of RD after silicone oil removal was evaluated. Results: 151 eyes received 360° laser retinopexy (completed intraoperatively in 93 eyes and postoperatively in 58 eyes, in nine of them after cataract extraction); 152 eyes served as controls. Silicone oil was removed from 139 laser-treated eyes (92.05%) and 129 controls (84.87%; NS). In the first group, 12 eyes (8.63%) developed an RD posterior to laser treatment (including the macula), three eyes (2.16%) had a localised posterior RD (treated by laser), and 14 (10.07%) had an RD anterior to the laser treatment. In the control group, RD occurred in 27 eyes (20.93%; p = 0.007). Conclusions: 360° laser retinopexy reduces the incidence of RD after silicone oil removal; it should be completed intraoperatively.

Ultrasound-Biomicroscopic Evaluation of Filtering Blebs after Laser Suture Lysis Trabeculectomy

Sometimes in glaucomatous patients treated with trabeculectomy there is no correlation between bleb shape and intra-ocular pressure (IOP). In this study we evaluated the ultrasound biomicroscopy (UBM) features of filtering blebs after laser suture lysis (LSL) trabeculectomy in order to analyse whether its ultrasound-biomicroscopic image can predict the function (IOP). Methods: The Humphrey ultrasound biomicroscope, using a high-frequency (50-Mhz) probe, provides high-resolution images of filtering blebs. A total of 103 filtering blebs after LSL trabeculectomy were analysed by UBM. Taking into account the characteristics of internal reflectivity and scleral flap, we classified the blebs into three groups (good, fair, poor) that indicate the bleb function and correlated this UBM pattern with the IOP control (good, borderline, failure). Results: There was a statistically significant corelation between the UBM classification of function and the IOP control level. Both well-functioning and failed trabeculectomies could be identified by UBM. The UBM images of eyes with good IOP control are characterized by better visibility of the route under the scleral flap and a low reflectivity inside the bleb. Conclusions: In accordance with previous studies, we believe that UBM can be a useful method to study and explain the mechanisms of filtering structures and, together with IOP control, to evaluate the bleb function.