Muna Al Oum

SLC45A2 mutation frequency in Oculocutaneous Albinism Italian patients doesn't differ from other European studies

BACKGROUND Oculocutaneous Albinism (OCA) is a heterogeneous group of inherited diseases involving hair, skin and eyes. To date, six forms are recognized on the effects of different melanogenesis genes. OCA4 is caused by mutations in SLC45A2 showing a heterogeneous phenotype ranging from white hair, blue irides and nystagmus to brown/black hair, brown irides and no nystagmus. The high clinic variety often leads to misdiagnosis. Our aim is to contribute to OCA4 diagnosis defining SLC45A2 genetic variants in Italian patients with OCA without any TYR, OCA2 and TYRP1 gene defects. MATERIALS AND METHODS After the clinical diagnosis of OCA, all patients received genetic counseling and genetic test. Automatic sequencing of TYR, OCA2, and TYRP1 genes was performed on DNA of 117 albino patients. Multiplex Ligation-dependent Probe Amplification (MLPA) was carried out on TYR and OCA2 genes to increase the mutation rate. SLC45A2 gene sequencing was then executed in the patients with a single mutation in one of the TYR, OCA2, TYRP1 genes and in the patients, which resulted negative at the screening of these genes. RESULTS SLC45A2 gene analysis was performed in 41 patients and gene alterations were found in 5 patients. Four previously reported SLC45A2 mutations were found: p.G100S, p.W202C, p.A511E and c.986delC, and three novel variants were identified: p.M265L, p.H94D, and c.1156+1G>A. All the alterations have been detected in the group of patients without mutations in the other OCA genes. CONCLUSIONS Three new variants were identified in OCA4 gene; the analysis allowed the classification of a patient previously misdiagnosed as OA1 because of skin and hair pigmentation presence. The molecular defects in SLC45A2 gene represent the 3.4% in this cohort of Italian patients, similar to other Caucasian populations; our data differ from those previously published by an Italian researcher group, obtained on a smaller cohort of patients.

Expression of VEGF-A, Otx homeobox and p53 family genes in proliferative vitreoretinopathy.

Introduction. Proliferative vitreoretinopathy (PVR) is a severe inflammatory complication of retinal detachment. Pathological epiretinal membranes grow on the retina surface leading to contraction, and surgery fails in 5% to 10% of the cases. We evaluated the expression of VEGF-A, Otx1, Otx2, Otx3, and p53 family members from PVR specimens to correlate their role in inducing or preventing the pathology. Methods. Twelve retinal samples were taken from patients affected by PVR during therapeutic retinectomies in vitreoretinal surgery. Gene expression was evaluated using quantitative real-time reverse transcriptase PCR analysis and immunohistochemistry, using four healthy human retinae as control. Result. Controls showed basal expression of all genes. PVR samples showed little or no expression of Otx1 and variable expression of VEGF-A, Otx2, Otx3, p53, and p63 genes. Significant correlation was found among VEGF-A, Otx2, p53, and p63 and between Otx1 and Otx3. Conclusions. Otx homeobox, p53 family, and VEGF-A genes are expressed in PVR human retina. We individuated two possible pathways (VEGF-A, Otx2, p53, p63 and Otx1 and Otx3) involved in PVR progression that could influence in different manners the course of the pathology. Individuating the genetic pathways of PVR represents a novel approach to PVR therapies.

Clinical analysis of macular edema with new software for SD-OCT imaging

Purpose To evaluate the clinical efficacy of user-friendly software for the measurement of intraretinal hyporeflective spaces expression of macular edema. Methods Fifteen consecutive patients with diabetic retinopathy with clinically significant macular edema were examined using conventional spectral domain optical coherence tomography (OCT). A new composite software application, OCT–measurement analysis tool (OCT-MAT), was developed to automatically process and analyze OCT B-scans by means of image acquisition, filtering, and elaboration, together with hyporeflective area recognition and measurement in μm2. The same macular areas were measured manually, and then compared to the measurements obtained by the automated OCT-MAT software. A statistical t test analysis was applied (statistical significance level at p<0.05). The repeatability and reproducibility coefficient for the automated software was computed using the Wilcoxon matched pair test (5% significance level). Results In all patients, the software effectively measured the number and extension of intraretinal hyporeflective spaces in μm2. The comparison between mean manual measurements and OCT-MAT measurements (0.478 ± 0.300 × 106 μm2 vs 0.471 ± 0.321 × 106 μm2) showed correct correspondence (p>0.05). Moreover, the OCT-MAT software showed good repeatability and reproducibility (coefficient below 3%). Conclusions OCT-MAT allows the precise measurement of macular edema in terms of the number of empty spaces and their size in all patients. Its daily clinical application might give precise information regarding the evolution of macular edema and the efficacy of therapy.

A teleconsultation network improves the efficacy of anti-VEGF therapy in retinal diseases

We investigated the care of patients with age-related macular degeneration (AMD) managed via a physician-to-physician teleconsultation network for ophthalmology. Eleven groups of ophthalmologists took part in the study. The groups were located in 10 cities across Italy. Each group was based on a Retina Centre located at a university or hospital, with one or two expert ophthalmologists (20 expert ophthalmologists in total). In each region containing a Retina Centre, 6-10 general ophthalmologists (94 ophthalmologists in total) referred patients via the network for a period of three months between June 2011 and December 2012. An automatic grading system quantified the risk of disease progression, and a remote booking system allowed the referring ophthalmologist to make appointments directly with the appropriate Retina Centre. There were 360 network patients and 318 control patients (consecutive patients undergoing usual care during the previous three months). The time delay before therapy was significantly shorter in the network patients (mean 5.5 days) compared with the usual care patients (mean 28.7 days; P < 0.0001). There was a significant improvement in visual acuity in the network patients after treatment (first visit = 0.29 logMAR; after treatment = 0.22 logMAR; P < 0.05). In contrast, there was no improvement in the usual care patients (first visit = 0.29 logMAR; after treatment = 0.27 logMAR; P > 0.05). The telemedicine network allows regional ophthalmologists to quantify the risk of disease progression, and to send patients to a Retina Centre quickly and easily, when required.

Ocular alignment and refraction in preterm children at 1 and 6 years old

Purpose To investigate cycloplegic refraction and ocular alignment in a population of preterm children at 1 and 6 years old. Patients and methods We included 261 preterm infants with a birth weight ≤1,500 g and a gestational age ≤32 weeks; there were 217 preterm infants (group 1), 28 preterm infants with mild retinopathy of prematurity (ROP) (group 2), and 16 preterm infants affected by severe ROP (group 3). Each patient underwent retinoscopy, ocular alignment assessment, and fundus examination at 1 and 6 years old. Results The prevalence of refractive errors and ocular alignment abnormalities at 1 year old in groups 2 and 3 compared to group 1 were, respectively (P<0.05): myopia 18% and 40.6% versus 6.9%; hyperopia 28.6% and 22% versus 39.2%; astigmatism 53.4% and 37.4% versus 53.9%; and strabismus 12.5% and 38% versus 5.3%. At 6 years old, they were, respectively (P<0.05): myopia 10.8% and 28.4% versus 7.4%; hyperopia 48.3% and 40.5% versus 62%; astigmatism 40.9% and 31.1% versus 30.6%; and strabismus 25% and 56.25% versus 11.5%. Conclusion At 6 years old, we observed increased rates of both hyperopia and strabismus in all groups compared to 1-year-old children. In preterm children with mild and severe ROP, we recorded increased rates of myopia and strabismus versus preterm children without ROP, and the risk of developing these disorders increased significantly with ROP severity. Astigmatism at 1 year old is not predictive of further development during growth. Patients born prematurely should be informed of the possible risks of ocular alterations due to refractive and ocular component changes.