Retinal vascular density in multiple sclerosis: a 1-year follow-up.

BACKGROUND AND PURPOSE: Vascular pathology is increasingly acknowledged as a risk factor for multiple sclerosis (MS). Vascular density (VD) is reduced in the eyes of patients with MS on optical coherence tomography (OCT) angiography. We performed a 1-year prospective study to estimate VD variations over time and possible clinical correlates. METHODS: A total of 50 patients with MS underwent spectral domain-OCT and OCT angiography at baseline and after 1-year follow-up. Mixed-effect linear regression models were used to assess variations of each OCT measure and its relation to treatment and clinical outcomes. RESULTS: We observed an increase in parafovea VD (coefficient, 1.147; 95% confidence interval, 0.081-2.214; P = 0.035). Reduction in parafovea VD was associated with increase in Expanded Disability Status Scale score (coefficient, -0.969; 95% confidence interval, -1.732/-0.207; P = 0.013). CONCLUSIONS: Retinal VD can improve over time in MS, particularly in patients experiencing disease stability. Longer follow-up, inclusion of early MS cases and combination with conventional markers of MS severity (i.e. brain atrophy) are needed to better define VD as a potential new biomarker.

Araujia sericifera New Host of Alfalfa mosaic virus in Italy.

Araujia sericifera Brot. (Fam. Apocynaceae) is an evergreen climbing plant native of South America, originally introduced in Europe as an ornamental. In spring 2012, virus-like symptoms including bright yellow mosaic of calico-type and leaf distortion were observed in three A. sericifera plants growing in an abandoned field located in Pomigliano d'Arco (Campania region, Italy). Leaves from the three plants were collected and examined using commercial antisera (Bioreba AG, Reinach, Switzerland) by double antibody sandwich (DAS)-ELISA against Cucumber mosaic virus (CMV), Alfalfa mosaic virus (AMV), and by indirect plate trapped antigen (PTA)-ELISA against potyviruses (Potygroup test). Only AMV was detected serologically in the three A. sericifera samples. The virus was mechanically transmitted from the ELISA-positive samples to four plants each of Chenopodium quinoa, C. amaranticolor, tobacco (Nicotiana tabacum cv. Xanthi nc), cowpea (Vigna unguiculata, cv. Black eyes), basil (Ocimum basilicum, cv. Gigante), and tomato (Solanum lycopersicum cv. San Marzano), using chilled 0.03 M sodium phosphate buffer, containing 0.2% sodium diethyldithiocarbamate, 75 mg/ml of active charcoal, and traces of Carborundum (600 mesh). Inoculated plants were kept in an insect-proof greenhouse with natural illumination and temperatures of 24 and 18°C day/night. Under these conditions, plants showed the following symptoms after 1 to 3 weeks, consistent with symptoms caused by AMV (1): chlorotic local lesions following by mosaic in C. quinoa and C. amaranticolor, reddish local lesions following by mosaic in cowpea, necrotic local lesions followed by systemic necrosis in tomato, bright yellow mosaic (calico type) in basil, and mosaic and strong deformation of the apical leaves in tobacco. The presence of AMV in ELISA-positive A. sericifera and host plants was further confirmed by conventional reverse transcription (RT)-PCR. Total RNAs were extracted with an RNeasy Plant Mini Kit (Qiagen, Hilden, Germany). RT-PCR was performed with the One-Step RT-PCR Kit (Qiagen) using primers for the coat protein gene (CP) previously used for the molecular characterization of AMV isolates (2). An Italian isolate of AMV from Lavandula stoechas (GenBank Accession No. FN667967) and RNA extracted from a healthy A. sericifera plant were used as positive and negative controls, respectively. An amplicon of the correct predicted size (∼750 bp) was obtained from each of the infected plants assayed, and that derived from A. sericifera isolate Ars2 was purified (QIAqick PCR Purification Kit, Qiagen), cloned in pGEMT easy vector (Promega, Fitchburg, WI) and sequenced (HF570950). Sequence analysis of the CP gene, conducted with MEGA5 software, revealed the highest nucleotide identity of 98% (99% amino acid identity) with the AMV isolate Tef-1 (FR854391), an isolate belonging to subgroup I (3). To our knowledge, this is the first report of AMV infecting A. sericifera in Italy. Since A. sericifera is considered an invasive plant, in continuous expansion to new areas in Italy and in other European countries, particular attention should be paid to the possibility that this species may play a role in the epidemiology of aphid-transmitted viruses such as AMV and CMV, representing a threat to susceptible crops growing nearby. References: (1) G. Marchoux et al. Page 163 in: Virus des Solanacées. Quae éditions, Versailles, 2008. (2) G. Parrella et al. Arch. Virol. 145:2659, 2000. (3) G. Parrella et al. Plant Dis. 96:249, 2012.

The role of OCT- angiography in predicting anatomical and functional recovery after endoscopic endonasal pituitary surgery: A 1-year longitudinal study.

PURPOSE: The purpose of this study was to investigate the changes in structural spectral-domain optical coherence tomography (SD-OCT), OCT Angiography (OCTA) parameters, and visual acuity, 1 year after endoscopic endonasal approach for the removal of an intra-suprasellar pituitary adenoma compressing optic chiasm and compare outcomes with 48 hours postoperative data. METHODS: Sixteen eyes of eight patients (4 males, 4 females, mean age 52 ± 11 years) were enrolled in this prospective study. The primary outcome was to evaluate the changes over time before and after surgery, analyzing the Best Corrected Visual Acuity (BCVA), Ganglion Cell Complex (GCC), Retinal Nerve Fiber Layer (RNFL) thicknesses, the retinal vessel density (VD) of Superficial Capillary Plexus (SCP), Deep Capillary Plexus (DCP), Radial Peripapillary Capillary (RPC) and the Foveal Avascular Zone (FAZ). The secondary outcome was to identify potential biomarkers that could predict visual acuity changes after 1-year follow-up. RESULTS: When comparing SD-OCT and OCTA measurements obtained after 1 year with those observed 48 hours after surgery, GCC and RNFL were significantly improved. After a significant reduction at 48 hours, GCC thickness showed a significant increase at 1 year after surgery (p = 0.007), while a significant restoration of RNFL thickness was found at 1 year (p = 0.005), as well as the VD of SCP, DCP, and RPC values. FAZ area did not change over time. BCVA significantly improved at each time after surgery (p = 0.037, p = 0.013). A statistically significant correlation was found between the preoperative BCVA, VD of SCP, DCP, RPC, and the postoperative BCVA at 1 year (p = 0.017, p = 0.029, p = 0.031, p = 0.023). CONCLUSION: SD-OCT and OCTA provide helpful information to identify the retinal structural and vascular improvements 1 year after surgery. OCTA parameters could serve as potential predictive markers for visual acuity recovery at long-term follow-up.

Once-per-cycle pegfilgrastim in breast cancer patients treated with docetaxel/epidoxorubicin/cyclophosphamide.

The incidence of neutropenia following combination chemotherapy is significant in breast cancer and impairs patients' quality of life. Colony-stimulating factors significantly decrease the risk of febrile neutropenia (FN). Aim of the present study was to assess the efficacy and safety profile of once-per-cycle pegfilgrastim in reducing FN in breast cancer patients treated with docetaxel (75 mg/m(2)), epidoxorubicin (75 mg/m(2)), cyclophosphamide (500 mg/m(2)) administered every 3 weeks. Thirty-five breast cancer patients were enrolled. Chemotherapy was administered in adjuvant, neoadjuvant and metastatic setting respectively in 26, 4 and 5 patients. Toxicity was monitored with programmed clinical evaluation and blood sampling. All patients completed the therapeutic programme consisting of six cycles for overall 210 cycles. The FN appeared in 6 out of 35 patients (17%), requiring dose reduction in 3 patients. Hypertransaminasemia was registered in two patients. In one patient pegfilgrastim administration was stopped because of skin hypersensitivity reaction. In conclusion, pegfilgrastim was able to maintain doses and timing of docetaxel/epidoxorubicin/cyclophosphamide in almost all breast cancer patients treated in this series. The reduced need for daily administration of colony-stimulating factors, blood sampling, antibiotic therapy and hospitalization has a significant impact in terms of both quality of life and pharmaco-economic evaluations.

Personalized treatment planning in eye brachytherapy for ocular melanoma: Dosimetric analysis on ophthalmic structure at risk.

PURPOSE: To evaluate the impact on dose distribution to eye organs-at-risk (eOARs) of a computed tomography (CT)-based treatment planning in eye plaque brachytherapy (EPB) treatment. METHODS: We analyzed 19 ocular melanoma patients treated with ruthenium-106 plaques to a total dose of 100 Gy to tumor apex using conventional central-axis-point dose calculation. Treatments were re-planned using the Plaque Simulator (PS) software implementing two different strategies: a personalized CT-eye-model (CT-PS) and a standard-eye-model (SEM-PS) defined by Collaborative Ocular Melanoma Study. Dice coefficient and Hausdorff distance evaluated the concordance between eye-bulb-models. Mean doses (Dmean) to tumor and eOARs were extracted from Dose-Volume-Histograms and Retinal-Dose-Area-Histogram. Differences between planning approaches were tested by Wilcoxon signed-rank test. RESULTS: In the analyzed cohort, 8 patients (42%) had posterior tumor location, 8 (42%) anterior, and 3 (16%) equatorial. The SEM did not accurately described the real CT eye-bulb geometry (median Hausdorff distance 0.8 mm, range: (0.4-1.3) mm). Significant differences in fovea and macula Dmean values were found (p = 0.04) between CT-PS and SEM-PS schemes. No significant dosimetric differences were found for tumor and other eOARs. The planning scheme particularly affects the OARs closest to the tumor with a general tendency of SEM-PS to overestimate the doses to the OARs closest to the tumor. CONCLUSION: The dosimetric accuracy achievable with CT-PS EPB treatment planning may help to identify ocular melanoma patients who could benefit the most from a personalized eye dosimetry for an optimal outcome in terms of tumor coverage and eOARs sparing. Further research and larger studies are underway.

Evaluation of choroidal tumors with optical coherence tomography: enhanced depth imaging and OCT-angiography features.

AimTo describe the vascular features of choroidal tumors using enhanced depth imaging (EDI), optical coherence tomography (OCT), and OCT-angiography.MethodsIn this prospective study, we evaluated 116 Caucasian patients with choroidal tumors (60 eyes with choroidal nevi, 40 with choroidal melanoma, 6 with choroidal hemangioma, 2 with optic disc melanocytoma, 6 with choroidal osteoma, and 2 with retinal metastases). Patients underwent a complete ophthalmic examination including bulbar echography, EDI-OCT, OCT-angiography, and multicolor imaging. Sixteen patients also underwent fluorescein and indocyanine angiography.ResultsThe left eye was more involved than the right eye. The mean tumor thickness was 1.23±0.17 mm in the 60 eyes with choroidal nevi; 2.75±0.83 mm in the 40 eyes with choroidal melanoma; 3.28±0.78 mm in the 6 eyes with retinal angioma; 2.02±0.001 mm in the 2 eyes with optic disc melanocytoma; 2.40±0.31 mm in the 6 eyes with choroidal osteoma; and last, 3.49±0.001 mm in the 2 eyes with retinal metastases. OCT-angiography showed: (i) a lack of blood flow in the outer retinal layer (ORL) and a normal choroid capillary layer in choroidal nevi and optic disc melanocytomas; (ii) a lack of blood flow in the ORL of choroidal metastases; and (iii) a dense irregular vascular network in the ORL and choroid capillary layers of choroidal melanomas, choroidal hemangiomas, and choroidal osteomas.ConclusionsOCT-angiography is a noninvasive reliable method with which to evaluate the vascularization of small choroidal tumors and may improve the diagnosis of these tumors.

Anatomical and functional retinal changes in multiple sclerosis.

AIMS: The aims of this study was to report anatomical changes of the ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thickness, and macular volume in patients with multiple sclerosis (MS). We also investigated the correlation between anatomical and functional changes in terms of visual acuity and macular sensitivity investigated and visual fields. METHODS: Prospective comparative study included 105 eyes of 53 consecutive patients. The patients were divided into two groups: group A included 56 eyes of 28 patients with diagnosis of MS; group B involved 49 eyes of 25 healthy patients. The examination included Goldmann tonometry, biomicroscopic and fundus oculi examination, retinography, GCC examination, circumpapillary RNFL (cpRNFL), and macular volume. The functional test included measurement of best-corrected visual acuity (BCVA), visual field, and MP. RESULTS: MS group showed a significant reduced GCC, cpRNFL, macular volume, BCVA, visual field, and macular sensitivity compared with the control group (P<0.001). This reduction was more representative (P<0.001) in patients with MS complicated by optic neuritis (ON). We found in the MS group a strong correlation between GCC thickness and macular volume (r(2)=0.59, P<0.001) and also between GCC and RNFL thickness (r(2)=0.48, P<0.001). There was also a correlation between macular sensitivity and macular volume reduction (r(2)=0.25, P<0.001) and also between RNFL and macular volume (r(2)=0.43, P<0.001). CONCLUSIONS: The significant statistical evidence and the strong correlation between anatomical and functional parameters support the use of OCT and MP in the evaluation, treatment, and follow-up of patients diagnosed with MS.

Evaluation of the retinal nerve fibre layer and ganglion cell complex thickness in pituitary macroadenomas without optic chiasmal compression.

PURPOSE: The aim of this prospective study was to measure the thickness of the circumpapillary retinal nerve fibre layer (cpRNFL) and the ganglion cell complex (GCC) using spectral domain optical coherence tomography (SD-OCT) in a cohort of consecutive de novo patients with pituitary macroadenomas without chiasmal compression. PATIENTS AND METHODS: Twenty-two consecutive patients with pituitary macroadenoma without chiasmal compression (16 men, 6 women, aged 45.2±14.6 years, 43 eyes) entered the study between September 2011 and June 2013. Among them, 31.8% harboured a growth hormone-secreting pituitary adenoma, 27.3% a prolactin-secreting pituitary adenoma, 27.3% a corticotrophin-secreting pituitary adenoma, and 13.6% a non-secreting pituitary tumour. Eighteen subjects (nine females, nine males, mean age 36.47±6.37 years; 33 eyes) without pituitary adenoma, with normal ophthalmic examination, served as controls. In both patients and controls, cpRNFL and GCC thicknesses were measured by SD-OCT. RESULTS: Patients were significantly older (P=0.02) than controls. Best corrected visual acuity, intraocular pressure, colour fundus photography, and automatic perimetry test were within the normal range in patients and controls. Conversely, cpRNFL (P=0.009) and GCC (P<0.0001) were significantly thinner in patients than in controls. The average GCC (r=0.306, P=0.046) significantly correlated with the presence of arterial hypertension. OCT parameters did not differ significantly between patients with a tumour volume above the median and those with a tumour volume below the median. CONCLUSION: Pituitary macroadenomas, even in the absence of chiasmal compression, may induce GCC and retinal nerve fibre layer thinning. SD-OCT may have a role in the early diagnosis and management of patients with pituitary tumours.

Metabolic effects of nitrendipine.

A randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and clinical efficacy of nitrendipine in the treatment of isolated systolic hypertension in elderly patients. The subjects were 20 elderly patients with isolated systolic hypertension who received 20 mg of nitrendipine or placebo daily for 60 days. In the nitrendipine-treated patients, both systolic and diastolic blood pressures were reduced significantly during treatment (from a mean of 180 to 155 mmHg and 92 to 80 mmHg); heart rate did not change significantly. Standard laboratory test results did not change in either group during treatment and results of a posttreatment oral glucose tolerance test were similar in the two treatment groups.

Optic nerve involvement in acute lymphoblastic leukemia.

Leukemic infiltration of the optic nerve is rare. We describe the diagnostic assessment and the outcome in two adult patients suffering from acute lymphoblastic leukemia with T phenotype. In both cases the leukemic involvement of the eye was observed as an isolated extramedullary relapse followed after several months by hematological relapse. CT and MRI scans were negative, while an A-scan echography of the eye clarified the diagnosis. Early radiotherapy caused recovery of visual acuity in one case. A-scan echography is the most sensitive investigation for the early recognition of ocular localization in acute leukemias.

Correlation between refractive and corneal topographic changes after photorefractive keratectomy for myopia.

PURPOSE: To compare videokeratographic and refractive data obtained before and after photorefractive keratectomy (PRK) for myopia. METHODS: Seventy-four eyes underwent PRK for myopia ranging from -2.50 to -17.00 D (mean, -7.76 +/- 3.17 D). All patients had videokeratography with the EyeSys instrument before, and 1 and 6 months after PRK, and the changes in three corneal power measurements (center of the ablation, apex, and effective refractive power) were compared with refractive changes. RESULTS: Changes obtained in the three corneal power measurements at 1 and 6 months were well correlated with manifest refraction (Pearson's coefficient ranged from 0.71 to 0.84). CONCLUSION: Power measurements obtained with corneal topography, as described above, are a reliable and objective method for the evaluation and follow-up of PRK, provided addition of an approximate 25% correcting factor.

Morning glory syndrome associated with marked persistent hyperplastic primary vitreous and lens colobomas.

A case of morning glory syndrome with striking persistence of primary vitreous is presented. The hypothesis that the syndrome is an expression of abnormal closure of the embryonic fissure is substantiated by the coexistence of lens colobomas. Furthermore, the marked primary vitreous hyperplasia shows the way in which persistence of primary vitreous influences the clinical expression with respect to optic pit and colobomas of the optic nerve.

Choroidal osteoma (osseous choristoma): an atypical case.

A case of choroidal osteoma presenting in a 22-year-old girl is reported. The tumour, unilateral and in a juxtapapillary site, appeared markedly elevated on the retinal plane, not flat or slightly elevated as in previous reports. Visual acuity was not affected, and there was a complete absence of subjective symptoms. Echography, fluorangiography, computerised tomography, and visual field tests were performed. Echography is the best method for identifying and differentiating this lesion from a malignant tumour.

First experience with a new echographic contrast agent.

The intravenous injection of an ultrasound contrast agent can enhance signals from blood flow. Broad toxicological and pharmaceutical studies in animals confirmed the safety and efficacy of an ultrasound contrast agent made of microparticles of galactose with stabilised microbubbles in watery suspension (SH U 508 A). In this paper 10 patients with different malignant orbital and ocular tumours have been evaluated with an echo colour Doppler machine before and after the injection of SH U 508 A. An enhancement of the Doppler signals in the lesions in different degrees has been detected. This echographic contrast agent seems to be very important not only in the evaluation of vascular lesions, but also in evaluating the effectiveness of radiotherapy in malignant tumours and could spread the echographic indications in several other ophthalmic fields.

Clinical features of X linked juvenile retinoschisis associated with new mutations in the XLRS1 gene in Italian families.

AIMS: To describe the clinical phenotype of X linked juvenile retinoschisis in eight Italian families with six different mutations in the XLRS1 gene. METHODS: Complete ophthalmic examinations, electroretinography and A and B-scan standardised echography were performed in 18 affected males. The coding sequences of the XLRS1 gene were amplified by polymerase chain reaction and directly sequenced on an automated sequencer. RESULTS: Six different XLRS1 mutations were identified; two of these mutations Ile81Asn and the Trp122Cys, have not been previously described. The affected males showed an electronegative response to the standard white scotopic stimulus and a prolonged implicit time of the 30 Hz flicker. In the families with Trp112Cys and Trp122Cys mutations we observed a more severe retinoschisis (RS) clinical picture compared with the other genotypes. CONCLUSION: The severe RS phenotypes associated with Trp112Cys and to Trp122Cys mutations suggest that these mutations determine a notable alteration in the function of the retinoschisin protein.

Comparison of three fungal laccases from Rigidoporus lignosus and Pleurotus ostreatus: correlation between conformation changes and catalytic activity.

The conformation changes in solution of three fungal laccases in different environmental conditions were examined by circular dichroism (CD) and electron paramagnetic resonance (EPR) spectroscopy. CD measurements indicate that the secondary structure of proteins depends slightly on the pH or ionic strength, though the presence of salt could interfere in the molecular recognition process between substrates and enzymes. The enzymes, however, are highly destabilized by prolonged exposure to low pH or high temperature. The observed unfolding of the proteins coincides with their inactivation and, in some cases, with precipitation. On the other hand, these conditions do not determine the disruption of the geometric arrangement of their metal centres, and this fact suggests that these centres represent the more stable core of the proteins.

Changes in glucose turnover parameters during muscular exercise: role of age.

In a study of ten young and seven elderly healthy men we have performed an oral glucose tolerance test (75 g) and employed a euglycemic hyperinsulinemic (0.25 mUx kg/min) glucose clamp technique in order to determine insulin sensitivity. This latter experimental protocol consisted of 120 min of euglycemic clamp followed by 60 min in which the clamp and a mild muscular exercise (35% VO(2) (max)) were combined. D-[(3)H]glucose infusion allowed a determination of the glucose turnover parameters. Our results show that in elderly subjects glucose disappearance rate and glucose metabolic clearance rate are significantly lower during both clamp, and clamp + muscular exercise studies. On the contrary, hepatic glucose production was similar under both conditions and was independent of age.

Exaggerated orthostatic hypotension as first sign of diabetic autonomic neuropathy in the elderly.

Long-standing diabetic subjects have an impaired sympathetic nervous system activity as a consequence of autonomic neuropathy. Moreover, in this latter group of subjects the parasympathetic rather than the sympathetic nervous system seems firstly impaired by glucose metabolism derangements. In the present study we show that, in aged diabetic subjects with a short duration of the disease (less than 5 years), and who are free from diabetic complications, it is possible to evidence a primary compromise of sympathetic rather than parasympathetic nervous system activity since a greater rate of orthostatic hypotension occurred. In the light of the well-known age-related changes in the physiopathology of cardiovascular activity, we hypothesize that in aged diabetic patients, even after a short duration of disease, sympathetic compromise precedes the derangement of parasympathetic nervous system activity.

Hydrocephalus combined with congenital cataract and microphthalmia.

We describe a case of bilateral microphthalmia with bilateral congenital cataracts associated with hydrocephalus in a 9-month-old girl with consanguineous parents. The differential diagnosis included: (1) congenital rubella syndrome; (2) congenital toxoplasmosis; (3) chromosome alterations; and (4) metabolic disease. However, negative clinical, laboratory, and instrumental investigations excluded all of these hypotheses. We stress the usefulness of echography in establishing whether or not infection has occurred during intrauterine life.

[A posterior dislocation of the lens in herpes zoster (author's transl)]. / Sur un cas de luxation spontanée postérieure du cristallin au cours d'un herpès zoster ophtalmique.

The authors report a case of posterior dislocation of the lens during the natural history of a clinical case of herpes zoster. An echographic B-scan study was carried out to reveal the position and the size and the shape of dislocated lens, together with its structure and that of ocular media. After a discussion on the possible aetiology of the lens dislocation it was considered due to herpes zoster disease, and are reported the possible mechanism of zonula alteration.