Comparison of growth factor and interleukin content of adult peripheral blood and cord blood serum eye drops for cornea and ocular surface diseases.

INTRODUCTION: Various blood-derived products have been proposed for the topical treatment of ocular surface diseases. The aim of the study was to compare the different content of Growth Factors (GFs) and Interleukins (ILs) in peripheral blood (PB-S) and Cord Blood (CB-S) sera. MATERIALS AND METHODS: Sera were obtained from 105 healthy adult donors (PB-S) and 107 umbilical/placental veins at the time of delivery (CB-S). The levels of epithelial-GF (EGF), fibroblast-GF (FGF), platelet-derived-GF (PDGF), insulin-GF (IGF), transforming-GF alpha (TGF-α,) and beta 1-2-3 (TGF-ß1-ß2-ß3), vascular endothelial-GF (VEGF), nerve-GF (NGF), Interleukin (IL)-1ß,IL-4,IL-6,IL-10, and IL-13 were assessed by Bio-Plex Protein Array System (Bio-Rad Laboratories, CA, USA). The Mann-Whitney test for unpaired data was applied to compare GFs and ILs levels in the two sources. The associations among each GF/IL level and the obstetric data for CB-S and hematological characteristics for PB-S were also investigated. RESULTS: The levels of EGF, TGF-α, TGF-ß2, FGF, PDGF, VEGF, NGF, IL-1B, IL-4, IL-6, IL-10, and IL-13 were significantly higher in CB-S compared to PB-S. Conversely, the levels of IGF-1, IGF-2, and TGF-ß1 were significantly higher in PB-S. The female sex and the weight of the child showed a significant association in predicting EGF and PDGF levels. CONCLUSION: A significantly different content in those GFs and ILs was demonstrated in the two blood sources. Since each GF/IL selectively regulates different cellular processes involved in corneal healing, the use of PB-S or CB-S should be chosen on the basis of the cellular mechanism to be promoted in each clinical case.

High-intensity focused ultrasound treatment in patients with refractory glaucoma.

PURPOSE: To assess the safety and efficacy of ultrasound coagulation of the ciliary body in refractory glaucoma. METHODS: This prospective multicenter interventional study was conducted in two Italian university-affiliated glaucoma centers: St. Orsola-Malpighi Teaching Hospital (Bologna, Italy) and University Eye Clinic of Genoa (Genoa, Italy). The main inclusion criterion was the diagnosis of glaucoma with a baseline intraocular pressure (IOP) ≥ 21 mmHg while on maximum topical and systemic medical hypotensive treatment. The EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France), which was employed in the study, uses miniaturized transducers to produce high-intensity focused ultrasound (HIFU). Treatment consisted of the sequential activation of each transducer lasting 4 s (group 1), 6 s (group 2) or 8 s (group 3). Hypotensive medications were interrupted after surgery and then prescribed only if postoperative IOP was ≥ 21 mmHg during follow-up visits. Patients were assessed before and 1, 7, 14, 30, 90 and 180 days after the procedure. Primary outcomes were the mean IOP reduction in the overall population and in groups 1, 2 and 3, and the rates of complete success, qualified success and failure. RESULTS: Thirty eyes (16 open-angle, 10 angle-closure and 4 neovascular glaucoma) of 30 patients were included. The mean preoperative IOP was 30.1 ± 10.5 mmHg. Twenty-nine patients completed the entire study follow-up; one patient exited from the study 3 months after HIFU and underwent trabeculectomy. At days 1 and 180, the mean IOP was significantly reduced (18.4 ± 7.2 and 20.2 ± 6.2 mmHg, respectively; all p < 0.0001). Group 3 patients (8-s ultrasound exposure time) showed a greater IOP reduction than the other two groups (-16.2 ± 8.3 for group 3 vs. -8.8 ± 6.6 for group 2 and -3.7 ± 6.5 for group 1; p = 0.02 and p < 0.001, respectively). Qualified and complete success was achieved in 23.3 and 46.7% of patients, respectively; treatment failure was recorded in 6.6%. CONCLUSIONS: Ultrasonic coagulation of the ciliary body is a safe and effective procedure for reducing IOP in refractory glaucoma. The increase in ultrasound exposure time appears to improve the response rate and the global efficacy of the procedure, with no detrimental effect on safety.

Genetic parameters and response to selection for growth in tambaqui.

Although the tambaqui (Colossoma macropomum) is the most cultivated native fish species in Brazil, estimated breeding values for growth traits are rarely used for selection of superior individuals in commercial fingerling production. This study aimed to estimate the (co)variance components of growth traits. Body weight, length and width of 2500 tambaqui were determined at tagging and at 6 and 12 months after tagging in a commercial breeding programme in Brazil. Heritability estimates were low for traits measured at tagging (0.10 to 0.19) and moderate to high for traits measured at 6 and 12 months (0.23 to 0.81). Common full-sib effects were high at tagging (>73%), low at 6 months and negligible at 12 months. Positive genetic correlations were found among growth traits at 12 months (0.84 to 0.99) and between growth traits at 6 and 12 months (0.80 to 0.92). These results show that animal selection can be performed at 6 months after tagging. Expected genetic gains for growth traits ranged from 8% to 31%. A simulation of the sex ratio was performed, as individuals did not reach sexual maturity during the experimental period. Because of the sexual dimorphism, more accurate heritability estimates were obtained when considering the female proportion to be 90% in the high-weight group. The findings indicate that it is possible to obtain considerable genetic gains in growth by selecting for growth traits. The development of a tool to determine the sex of animals at early stages can improve the response to selection in tambaqui.

Quantitative Approach for the Analysis of Fusional Convergence Using Eye-Tracking and SacLab Toolbox.

Fusional vergence is a disjunctive movement of the eyes that is made in order to obtain single vision. The aim of the study was to provide a quantitative and objective approach for analyzing the fusional convergence response using eye tracking (ET) technology and automatic data analysis provided by the intuitive SacLab toolbox previously developed by our group. We evaluated the proposed approach in a population of 26 subjects with normal binocular vision, who were tested with base-out prisms (magnitudes 4Δ, 6Δ, and 10Δ) in order to elicit fusional convergence response. Eye movements were recorded using the Viewpoint ET and analyzed using SacLab. Parameters describing both the vergence and the version components of the fusional response (convergence duration, CD; peak convergence velocity, PCV; number of intrusive saccades, NS; and mean saccadic amplitude, MSA) were automatically calculated and provided to clinicians for an objective evaluation. Results showed that the number of subjects achieving fusional convergence decreased with prism magnitude. For subjects achieving fusion CD and PCV increased significantly (p < 0.05) when increasing the prism magnitude. For NS and MSA, there were no significant changes when passing to 6Δ, but a significant increase resulted when passing to 10Δ (p < 0.05). Noninvasive ET associated with the intuitive SacLab toolbox may represent a valid option to objectively characterize the fusional vergence response in clinical setting. The analysis may be extended to patients with vergence disorders.

Role of magnetic resonance imaging in heavy eye syndrome.

PurposeThe aim of this study is to assess the importance of magnetic resonance imaging (MRI) before surgery in highly myopic patients, evaluating the capability of imaging to identify muscles displacement and orbital pulley abnormalities and their role in the pathogenesis of heavy eye syndrome (HES).MethodsWe reviewed the medical records and high-resolution orbital MRIs of highly myopic adults with HES, who underwent surgery for strabismus at the Sant'Orsola-Malpighi University Hospital of Bologna from January 2007 to June 2016. The measure of the angle of dislocation between lateral rectus and superior rectus and lateral rectus-superior rectus band (LR-SR band) were evaluated on coronal MRI imaging.ResultsA total of 54 patients with HES were evaluated by MRI. Mean axial length was 30.5±3 mm. Mean distance esotropia was 49.2±14.4 prism diopters (PD) and the mean hypotropia was 4.3±4.4 PD. All subjects exhibited severe superotemporal globe prolapse that displaced the lateral rectus inferiorly and the superior rectus muscle medially with mean angle of dislocation of 167.5±12.9° on MRI. The LR-SR band was thinned in 56 eyes, ruptured in 8 and not evaluable in 1 case.ConclusionsIn our study, we detected muscles displacement in all subjects and we discovered alteration of the LR-SR band in patients with HES, suggesting a possible role in the pathogenesis of this disease. The evaluation of preoperative orbital MRI imaging in patients with highly myopic strabismus is helpful to detect different anatomical etiology and eventually to drive the choice of appropriate surgery.

Ocular surface analysis in hematological patients before and after allogeneic hematopoietic stem cell transplantation: implication for daily clinical practice.

PurposeTo evaluate ocular surface parameters before and after hematopoietic stem cell transplantation (HSCT) and to correlate them with clinical and transplant variables.MethodsThis is a retrospective analysis of data from 93 patients affected by hematological malignancies undergoing HSCT. Values from Ocular Surface Disease Index, Schirmer test, Break-up Time, ocular surface staining, and Meibomian Gland Dysfunction score obtained before HSCT and 3-6 months after were retrieved from charts. Diagnosis and staging of dry eye (DE) disease was performed according to Dry Eye WorkShop criteria. Graft-versus-host-disease (GVHD) was classified according to the NIH criteria. Odds ratios for DE onset after HSCT were estimated for demographic, ocular, hematological and transplant variables.ResultsDE was diagnosed before HSCT in 50 (53%) of the patients, mostly of hyperevaporative profile. After HSCT, all ocular parameters significantly worsened with no change in DE profile. A 51% incident cases (22 of the 43 non-DE subjects) were reported. Increasing recipient age and female sex, higher CD34+ cells infused, donor-recipient sex mismatch (males receiving from females), related donors, and peripheral blood cells as stem cell source were associated with a significant higher incidence of DE after HSCT. Systemic chronic GVHD was diagnosed in 42% while ocular GVHD in 35.5% of the patients, which decreased to 12% when taking into account only incident cases.ConclusionsHigh DE prevalence was shown already before HSCT. A pre-HSCT ocular surface assessment is recommended for early DE diagnosis and treatment. This new protocol also influences the prevalence of ocular GVHD.

A proposal of new ocular items in Sjögren's syndrome classification criteria.

OBJECTIVE: To verify whether ocular surface tests other than those included in primary Sjögren's syndrome (SS-I) classification criteria (Schirmer I, Break up Time, vital dye staining) may contribute to SS I diagnosis. METHODS: Two hundred and sixty-two patients (78 SS-1, 91 non-SS autoimmune diseases, 93 Sicca syndrome) filled a validated questionnaire on symptoms and were evaluated by Schirmer test without (Schirmer I) and with (Jones test) topical anaesthesia, Break Up Time (BUT), corneal aesthesiometry, tear clearance rate, vital dye (lissamine green) staining, impression conjunctival cytology, concentration of tear lysozyme and lactoferrin. Thresholds were selected from Receiver Operating Curves; sensitivity, specificity, likelihood ratio (LR+), predictive values were calculated for each test. A logistic regression model was constructed representing the best diagnostic index for SS. RESULTS: Data showed a poor diagnostic performance of Schirmer test I (LR+ 1.38) and BUT (LR+ 1.05); results from lissamine green staining may be unreliable due to incorporation bias. Tear lactoferrin (LR+ 4.52), Jones test (LR+ 6.24), tear lysozyme (LR+ 8.0), symptom questionnaire (LR+ 8.62), tear clearance rate (LR+ 18.73) and corneal aesthesiometry (LR+ 20.96) exhibited high diagnostic performance also taken together in the regression model. CONCLUSION: Because many of the tests we have screened in this study can be carried out by a trained ophthalmologist in any clinical setting, we recommend that ocular surface impairment is studied with the combination of tests proved to be helpful for the SS I diagnosis.

Critical flicker-fusion frequency as an indicator of human receptive field-like properties.

A psychophysical function, believed to reflect receptive field-like properties, is described. It is based on the determination of the critical flicker fusion frequency (CFF) of a tiny test target, centered on a round background of fixed luminance, the size of which is varied as the test parameter. Under optimal conditions, the maximal obtained frequency difference is 10 Hz. This function is compared with the so-called sustained-like function, with which it has some common aspects. Additionally, a portion of the flicker-based function apparently derives from a non-sustained-like source.

Anomalous retinal correspondence. Monocular and binocular visual evoked responses.

Monocular and binocular flashed visual evoked responses (VERs) were recorded in two normal subjects, two patients with partially accommodative refractive small-angle esotropia, and two patients with residual small-angle esotropia. Without optical correction the binocular VER of the patients with partially accommodative esotropia was equal to the monocular one, thus confirming suppression of the deviated eye as found with the striated glasses test. In the two patients with residual small-angle deviation and in the two with partially accomodative strabismus wearing an optical correction to reduce the angle of deviation, the binocular VER was larger than the monocular one. These patients showed anomalous retinal correspondence (ARC). Although the binocular recording of strabismic patients was smaller than the one obtained in normal subjects, still a cortical binocular interaction was found. In the subjects tested, ARC is objectively demonstrated to sustain an anomalous type of binocular vision.

Simultaneous measurement of the amount of muscle recession and transposition. A new caliper.

A Castroviejo caliper was modified, adding another caliper to one arm to be able to measure contemporaneously the amount of muscle recession and transposition.

Abnormal spatial localization in patients with herpes zoster ophthalmicus. Evidence for the presence of proprioceptive information.

Patients with herpes zoster of the ophthalmic branch of the trigeminal nerve and normal ocular motility were examined. They were asked to point to targets without the sight of their own hand. Significant errors were found on the affected side. Proprioceptive information of the extraocular muscles is assumed to travel in the trigeminal nerve, and these results thus suggest the existence of peripheral afferent signals influencing eye-hand coordination.

Plagiocephaly causing superior oblique deficiency and ocular torticollis. A new clinical entity.

Unilateral coronal suture stenosis provokes a shortening of the orbital roof of one side. It is argued that the effectiveness of the superior oblique muscle is reduced because of reduced length of its unreflected part and because of the increased angle between the reflected part of the tendon and ocular axis. This condition causes a clinical picture of superior oblique palsy, with ocular torticollis. We report four cases of this newly described clinical entity with various degrees of involvement of ocular motility.

Visual resolution in a patient exhibiting a visual fatigue or saturation-like effect: probable multiple sclerosis.

A rapid visual resolution test conducted on available equipment reveals the presence of rapid falloff in acuity in a case of probable multiple sclerosis. Intense large field illumination was used, and grating acuity was tested using laser red light. The effect is so large that minor anomalies (not subjectively appreciated) or the residuum of earlier minor attacks of retrobulbar optic neuritis can be readily detected. A related "visual fatigue or saturation-like syndrome" was described earlier. In bright environments these patients' vision fades. Briefly closing the eyes restores visual sensitivity. Providing filters or lowering the light level tends to maintain vision. This test must be studied intensively. It offers a noninvasive simple means of showing underlying anomalies in neural conduction of the visual signal. Such anomalies can be prognostic and previously have been revealed only with sophisticated electrophysiological techniques.

Lack of alternation in patients treated for strabismic amblyopia.

Of a series of 57 formerly amblyopic patients who attained equal visual acuities (20/20 or better in each eye), only 29 were able to alternate after treatment. The oldest patient was 5 years old. The pattern visual-evoked response of the previously amblyopic eye in nonalternators showed a reduced amplitude as compared with that of the sound eye. This probably occurred because of a reduced number of cortical cells subserving the formerly amblyopic eye. Lack of alternation may be the result of cortical competition. More cortical cells are connected to the originally normal eye even after successful treatment of the amblyopic eye in the nonalternating patient.

Cytidine-5'-diphosphocholine improves visual acuity, contrast sensitivity and visually-evoked potentials of amblyopic subjects.

PURPOSE: Cytidine-5'-diphosphocholine (CDP-choline) therapy is currently used to improve the consciousness level in patients with brain lesions and as a complement to levodopa therapy in Parkinson's disease. Recently, the substance has been shown to improve the visual acuity (VA) of both eyes of adults with amblyopia. This study aims at establishing whether Contrast Sensitivity (CS) and visually-evoked potentials (VEPs) also change after CDP-choline treatment. METHODS: VA, CS, and VEPs were measured in a group of amblyopic volunteers (n = 10, mean age 24.8 years) before treatment with Neuroton (CDP-choline, 1 g/day intramuscularly [IM] for 15 days) and the day after termination of the same. CS was evaluated, using a forced-choice, automatic procedure (QUEST: Watson and Pelli, 1983). Steady-state VEPs were recorded in response to counterphased (8 Hz) sinusoidal gratings (2 c/deg) of different contrasts. RESULTS: On average, after treatment, VA improved 1.4-1.5 lines in the amblyopic eyes and 0.4 lines in the normal eyes. CSs improved in both dominant and amblyopic eyes by about 3 dB. VEPs increased in amplitude (about 30%) and advanced in phase (about 0.2 pi rad). Amplitude and phase changes were not correlated. CONCLUSIONS: Treating adult amblyopes with CDP-choline has the effect of improving their VA, CS and VEPs. Changes occur in both eyes, although to different extents, and resemble those previously reported for levodopa treatment.

Bilateral Parry-Romberg syndrome associated with retinal vasculitis.

PURPOSE: To describe an unusual case of bilateral progressive facial hemiatrophy (Parry-Romberg syndrome (PRS)) associated with retinal vasculitis. METHODS: In a 37-year-old man with bilateral PRS, retinal vasculitis of the right eye was evident on fundus examination and fluorescein angiography. Right temporalis muscle biopsy and needle electromyography of the masseter muscles were performed. The patient underwent immunosuppressive therapy and retinal laser photocoagulation. RESULTS: Biopsy specimens showed large fibrosis with focal lymphohistiocytic infiltration of the muscle fibers. Electromyographic findings are consistent with a primary muscle disease. Visual acuity improved from 20/25 to 20/20 in the right eye with a follow-up of one year. CONCLUSIONS: The evidence of retinal vasculitis and the histologic findings of facial changes observed in this PRS case could support the pathogenetic model of a chronic inflammatory process as a plausible explanation for progressive facial hemiatrophy.

Visual recognition time in strabismus: small-angle versus large-angle deviation.

PURPOSE: To measure the possible differences in monocular detection time of a threshold visual acuity stimulus (recognition time [RT]) between patients with small-angle and large-angle strabismus. METHODS: Ten patients with free alternating esotropia were tested (10 to 18 years old): five with small-angle esotropia (< or = 7 degrees), five with large-angle esotropia (15 degrees to 20 degrees). Six age-matched normal subjects served as controls. The RT of the threshold stimulus was measured in both eyes sequentially for stimuli presented in the center of a computer monitor (RT 1). Moreover, we measured the time necessary for identifying the same threshold visual acuity stimulus generated on the computer screen in the moment in which fixation is taken up by one eye after occlusion of the second eye (RT 2). Using the same setting, RT was also measured monocularly in all strabismic and normal subjects who were originally looking at a luminous fixation point positioned horizontally at 6.5 and 15 degrees from the center of the monitor (RT 3). RESULTS: The multivariate analysis of variance for repeated measures indicated that there was no statistical difference in RT 1 between groups. The mean RT 2 was significantly longer (p<0.001) in large-angle strabismic eyes when compared with that of normal control eyes. The mean RT 2 in small-angle strabismic eyes did not differ significantly from that of normal eyes. Finally, RT 3 (both at 6.5 degrees and 15 degrees of eccentricity) did not show any significant difference in the three different study groups. CONCLUSIONS: The authors hypothesized that alternating strabismus patients may have a significant advantage in maintaining a small-angle deviation, as a large-angle deviation would require longer RT in the moment the deviated eye takes up fixation. It can be speculated that the extension of re-fixation movement, obviously shorter in small-angle strabismus patients, is the main factor responsible for longer RT occurring in large-angle strabismus patients.

Amount of aniseikonia compatible with fine binocular vision: some old and new concepts.

Random Dot Stereograms (RDS) are useful, but are sometimes misleading in assessing the degree of binocular cooperation in the presence of aniseikonia. RDS may give positive results up to 15% aniseikonia, whereas a fine central binocularity is not possible with more than 5% image-size difference. It is suggested that stereopsis may not be the only parameter to test; stress is given to the importance of peripheral motor fusion in maintaining the eye alignment.

Critical age of botulinum toxin treatment in essential infantile esotropia.

PURPOSE: To assess the results of botulinum toxin treatment in 60 consecutive children with essential infantile esotropia. METHODS: Bilateral simultaneous injection of botulinum toxin into the medial rectus muscle was performed in 60 patients under direct visualization with an "open sky" technique. Fluothane/sevoflurane insufflation anesthesia was used. Each patient underwent a single bilateral botulinum toxin injection. Patient age at the time of injection ranged from 5-8 months. RESULTS: Mean patient age at the time of treatment for the 88% of patients who gained a good alignment (within +10 prism diopters [delta] of residual esotropia) was 6.5 months, while mean patient age at time of injection for the 12% of patients who were undercorrected or the deviation relapsed was 7.8 months. Follow-up averaged 5.2 years (range: 2-9 years, SD 2). No variation of the angle of strabismus was observed after 6 months from injection. In some patients with hyperopic refraction, plus lens corrections were prescribed during follow-up to stabilize the alignment. CONCLUSION: Botulinum toxin can be effective in essential infantile esotropia when children are treated by age 7 months.

[Ocular surface analysis in patients affected with rheumatic diseases]. / Analisi della superficie oculare in pazienti affetti da malattie reumatiche.

OBJECTIVE: The international criteria for primary Sjögren's Syndrome (SS I) diagnosis (Vitali et al. 2002) include the Schirmer test I and vital dye staining as tests for ocular surface involvement, but diagnosis can be reached also when the item for ocular signs is not satisfied. The purpose of our study was to evaluate the ocular surface in patients with Sjögren's Syndrome, non-Sjögren's autoimmune diseases and Sicca Syndrome, to understand whether the SS I diagnosis can be targeted also on other tests related to the ocular surface status. METHODS: Clinical and cytological data were collected from 122 patients: 40 patients had diagnosis of Primary Sjögren's Syndrome, 51 a non Sjögren's autoimmune disease and 31 had symptoms of dry eye. A validated questionnaire on symptoms was filled by each patient; clinical tests included: Schirmer test I, Jones test, Ferning test, Break Up Time, corneal aesthesiometry, tear clearance test, vital dye staining of the ocular surface, scraping and impression conjunctival cytology. Data were statistically evaluated by using SPSS software and Mann-Whitney analysis on unpaired data. RESULTS: Data show that the subjective symptoms score, tear production, tear turnover, corneal sensitivity and ocular surface integrity are affected in SS I patients, with a statistically significant difference when matched to the other two groups. CONCLUSIONS: Our results suggest to enlarge the spectrum of ocular surface analysis, to support and orient a differential diagnosis among the autoimmune diseases.