Maurizio Fossarello

Tubby-like protein-1 mutations in autosomal recessive retinitis pigmentosa.

We suggest that antimony is able to enter the body from environmental sources other than cot mattresses and their covers. We determined antimony concentrations in babies with SIDS; stillborn babies; babies who died aged less than a week; and babies who died aged under 1 year. Samples of liver were collected at necropsy at the Hammersmith Hospital, London. Laboratory analysis was performed blind to group, and the code was not broken till all chemical analyses had been completed. Hepatic antimony concentration was determined in triplicate using hydridegeneration Atomic Absorption Spectroscopy (AAS). We took precautions to avoid any possible contamination of samples with antimony. There was a wide variation in hepatic antimony concentrations within the group, particularly in the oldest control group where there was one infant with a hepatic antimony concentration of 98 ng/g. Despite these wide fluctuations there were no statistically significant differences between antimony concentrations in the four groups (see table). These results do not support Richardson’s theory that antimony exposure is a cause of SIDS. However, it is apparent that there is evidence of both prenatal and postnatal exposures to antimony. Furthermore, the presence of antimony in the liver of stillborn babies suggests that antimony was accumulating during fetal life. Antimony from industrial sources is an environmental pollutant that is present in the food chain and in the atmosphere. It accumulates in the body, particularly in the skeleton. 5 It is possible that during pregnancy and lactation when enhanced bone remodelling of the maternal skeleton occurs, antimony may be released into maternal blood, and will thus be free to cross the placenta and accumulate in fetal tissues.

Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10−8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10−11) and 8q12 (minimum p value 1.82×10−11) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. “Replication-level” association was also seen between hyperopia and 12 of Kiefer et al.s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Ocular refraction: heritability and genome-wide search for eye morphometry traits in an isolated Sardinian population

No genes influencing oculometric phenotypes have yet been identified, despite it being well known that eye morphometry is involved in refraction and that genetics may play an important role. We have therefore performed a heritability analysis and genome-wide search (GWS) of biometric ocular traits in an isolated Sardinian population, assessing the genetic contribution and identifying the associated genetic loci. A complete eye examination including refraction and ocular biometry measurements such as axial length (AL), anterior chamber depth (ACD) and corneal curvature (CC), was performed on 789 subjects. Heritability analysis was carried out by means of parent–offspring regression and variance component models. Univariate and bivariate linkage analysis was performed by using 654 microsatellite markers spanning the genome. CC showed a mean heritability of 57%. AL and ACD were found to have significantly different variances (P<0.01) in males and females, so that heritability was calculated separately for each sex. AL had an estimated heritability in females of 31% and in males of 60%, whereas ACD had an estimated heritability of 47% in females and of 44% in males. In the GWS, the most suggestive evidence of linkage was identified on chromosome 2 for AL (LOD 2.64), on chromosome 1 for ACD (LOD 2.32) and on chromosomes 7, 2 and 3 for CC (LOD 2.50, 2.44 and 2.34, respectively). High heritability of eye morphometry traits was thus revealed. The identified loci are the first linkage signals available in ocular biometry. Notably, the observed significant differences in parental transmission deserve further study.

Photodynamic therapy of corneal neovascularization with verteporfin

Purpose. To describe the effect of photodynamic therapy (PDT) using verteporfin (Visudyne®) on corneal neovascularization (CNV) in two patients. Methods. Two patients with corneal neovascularization were treated with a nonthermal laser light at 689 nm delivered 15 min after an intravenous infusion of verteporfin. Postoperative outcome of neovascularization was followed clinically (inflammation, intraocular pressure, and visual acuity) and photographically [color photographs and corneal fluorescein and indocyanine green (ICG) angiography] for a minimum of 6 months. Results. Successful photothrombosis of corneal neovascularization was obtained immediately after treatment in the two patients, and regression was verified by corneal fluorescein and ICG angiography. In one case, partial vessel recanalization was observed after 1 month, and treatment was repeated, with complete regression of new vessels. No relevant side effects were observed in our cases. Conclusions. PDT with verteporfin is an effective and safe procedure indicated for patients with corneal neovascularization; however, multiple sessions may be required.

Molecular and Clinical Characterization of Albinism in a Large Cohort of Italian Patients

PURPOSE The purpose of this study was to identify the molecular basis of albinism in a large cohort of Italian patients showing typical ocular landmarks of the disease and to provide a full characterization of the clinical ophthalmic manifestations. METHODS DNA samples from 45 patients with ocular manifestations of albinism were analyzed by direct sequencing analysis of five genes responsible for albinism: TYR, P, TYRP1, SLC45A2 (MATP), and OA1. All patients studied showed a variable degree of skin and hair hypopigmentation. Eighteen patients with distinct mutations in each gene associated with OCA were evaluated by detailed ophthalmic analysis, optical coherence tomography (OCT), and fundus autofluorescence. RESULTS Disease-causing mutations were identified in more than 95% of analyzed patients with OCA (28/45 [62.2%] cases with two or more mutations; 15/45 [33.3%] cases with one mutation). Thirty-five different mutant alleles were identified of which 15 were novel. Mutations in TYR were the most frequent (73.3%), whereas mutations in P occurred more rarely (13.3%) than previously reported. Novel mutations were also identified in rare loci such as TYRP1 and MATP. Mutations in the OA1 gene were not detected. Clinical assessment revealed that patients with iris and macular pigmentation had significantly higher visual acuity than did severe hypopigmented phenotypes. CONCLUSIONS TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency than that found in other populations. Clinical analysis revealed that the severity of the ocular manifestations depends on the degree of retinal pigmentation.

Intravitreal bevacizumab as a treatment for choroidal neovascularisation secondary to myopia: 4-year study results

OBJECTIVES To report long-term follow-up results from intravitreal bevacizumab (IVB) treatment of choroidal neovascularisation (CNV) secondary to pathologic myopia (PM). DESIGN The study was designed as a retrospective analysis of consecutive patients presenting with PM. PARTICIPANTS Twenty-one eyes were examined from 20 different patients. METHODS The study was designed as a retrospective, consecutive, nonrandomised, interventional case series. Twenty-one eyes from 20 patients with CNV secondary to PM who were treated with bevacizumab were followed for a maximum of 52 months. Best-corrected visual acuity (BCVA), optical coherence tomography, and fluorescein and indocyanine green angiography were performed on each patient at baseline presentation and every 3 months thereafter for the entire follow-up period. The continuation therapy was based on dosing as needed regimen (PRN) for treatment assessment. RESULTS Overall, 15 (71.4%) of the 21 eyes studied demonstrated an improvement of ≥ 1 line on the Snellen chart. A total of 3 (14.3%) eyes showed no change with this analysis, and 3 (14.3%) eyes lost 1 line of discrimination. After the 4-year study period, fluorescein angiography suggested absence of angiographic leakage or fibrotic lesions in 15 eyes, and 3 eyes showed partial regression of myopic CNV. The remaining 3 eyes demonstrated total regression of CNV. CONCLUSIONS Intravitreal bevacizumab appears to be an effective therapy for myopic CNV and its benefit may persist in a long-term follow-up, on the basis of PRN treatment compared to the natural history of the disease.

Qualitative and quantitative analysis of filtering blebs with optical coherence tomography

OBJECTIVE To provide a qualitative and quantitative analysis of filtering blebs with optical coherence tomography (OCT) in patients after primary trabeculectomy. DESIGN Evaluation of diagnostic technology. PARTICIPANTS We retrospectively studied 20 eyes of 20 patients who had a fornix-based flap in primary trabeculectomy: 14 with mitomycin C (MMC) and 6 without MMC. METHODS Filtering blebs were examined using 2 types of OCTs working at a wavelength of 840 and 1310 nm. In this study, we analyzed both the OCT morphologic pattern and the internal structures of blebs, including bleb wall thickness, scleral flap thickness, and the route under the scleral flap, and quantified the reflectivity of the intrableb area. RESULTS Blebs were classified according to the Hirooka scheme in 3 OCT morphologic patterns: cystoid, diffuse, and layer type. The MMC was associated with the surgical success (100%). A significant association was found between good functionality and cystoid type with both devices: 840-nm OCT (p = 0.02) and 1310-nm OCT (p = 0.04). A significant difference in morphologic patterns was found using the 2 OCTs. There were no significant differences between successful and unsuccessful filtering surgery for intrableb structures. The reflectivity of filtering blebs correlated very well to the postoperative intraocular pressure (IOP; R(2) = 0.90; p < 0.001) and to the reduction of IOP (R(2) = 0.58; p = 0.001). Our method to quantify the reflectivity showed a significant degree of intergrader consensus (intraclass correlation coefficient = 0.99; p < 0.001). CONCLUSIONS Although 840-nm OCT was not developed to assess the anterior segment, it may be considered a useful tool to evaluate the functionality of blebs in the postoperative period.

Photodynamic therapy of pterygium with verteporfin: a preliminary report.

Objective: To assess the efficacy and safety of treating pterygia by photodynamic therapy (PDT) with verteporfin (Visudyne®). Materials and Methods: Ten consecutive patients with primary, recurrent, or secondary pterygium, refusing excisional surgery, were treated with a 689-nm laser delivered directly onto the pterygium after verteporfin infusion. Postoperative outcome was followed clinically and photographically for a minimum of 3 months. Results: Successful photothrombosis of pterygium vascularization was obtained immediately after treatment in all cases. After 1 month, revascularization of pterygia was observed in 70% of cases, and treatment was repeated after a 3-month interval. Regression or stabilization of pterygia was manifested by a scarring reaction of the corneal apex with complete or partial disappearance of vascularity. No relevant side effects were observed in our series. Conclusion: PDT with verteporfin is a safe procedure to arrest the growth of pterygia. It is indicated for patients with a low- or medium-grade pterygium that refuse a surgical approach; however, multiple sessions may be required.

23Na NMR investigation of human lenses from patients with cataracts

23Na NMR Lens Cataract

A novel technique of contrast-enhanced optical coherence tomography imaging in evaluation of clearance of lipids in human tears.

Purpose The aim of this work was to gather preliminary data in different conditions of healthy eyes, aqueous tear deficient dry eyes, obstructive meibomian gland disease (MGD) and non-obvious obstructive MGD (NOMGD) individuals, using a new, contrast-enhanced optical coherence tomography (OCT) imaging method to evaluate the clearance of lipids in human tears. Methods Eighty-two adult patients presenting with complaints of ocular irritation were studied for abnormalities of the ocular surface and classified as healthy (n = 21), aqueous tear deficient dry eyes (n = 20), obstructive MGD (n = 15) and NOMGD (n = 26) individuals. A lipid-based tracer, containing an oil-in-water emulsion, was used to obtain an enhanced OCT imaging of the lower tear meniscus. After instillation, a dramatic initial increase of reflectivity of the lower tear meniscus was detected by OCT, followed by a decay back to baseline values over time. Based on this finding, the clearance of lipids was measured in real-time by Fourier-domain anterior segment OCT. Results The differences in the clearance of lipids among the four groups as well as the correlations between symptom questionnaire score, standardized visual scale test, fluorescein break-up time, ocular surface fluorescein staining score, Schirmer I test scores were found to be statistically significant. The individual areas under the curve of the clearance of lipids calculated by the receiver operating characteristic curve technique ranged from 0.66 to 0.98, suggesting reliable sensitivity and specificity of lipid-enhanced OCT imaging. Conclusions This new technique of contrast-enhanced OCT imaging of the tear film following lipid-based tracer instillation provides a measure of the clearance of lipids. The quantitative values found are in agreement with other methods of evaluation of the lacrimal system. An improvement of the clinicians ability in the diagnosis and understanding of abnormalities of the ocular surface may be achieved by this simple approach.