Protocol-driven adjustment of ocular hypotensive medication in patients at low risk of conversion to glaucoma

AIM: To investigate the safety and potential savings of decreasing medication use in low-risk patients with ocular hypertension (OH).
METHODS: Patients with OH receiving pressure-lowering medication identified by medical record review at a university hospital underwent examination by a glaucoma specialist with assessment of visual field (VF), vertical cup-to-disc ratio (vCDR), central corneal thickness and intraocular pressure (IOP). Subjects with estimated 5-year risk of glaucoma conversion <15% were asked to discontinue ≥1 medication, IOP was remeasured 1 month later and risk was re-evaluated at 1 year.
RESULTS: Among 212 eyes of 126 patients, 44 (20.8%) had 5-year risk >15% and 14 (6.6%) had unreliable baseline VF. At 1 month, 15 patients (29 eyes, 13.7%) defaulted follow-up or refused to discontinue medication and 11 eyes (5.2%) had risk >15%. The remaining 69 patients (107 eyes, 50.7%) successfully discontinued 141 medications and completed 1-year follow-up. Mean IOP (20.5±2.65 mm Hg vs 20.3±3.40, p=0.397) did not change, though mean VF pattern SD (1.58±0.41 dB vs 1.75±0.56 dB, p=0.001) and glaucoma conversion risk (7.31±3.74% vs 8.76±6.28%, p=0.001) increased at 1 year. Mean defect decreased (-1.42±1.60 vs -1.07±1.52, p=0.022). One eye (0.47%) developed a repeatable VF defect and 13 eyes (6.1%) had 5-year risk >15% at 1 year. The total 1-year cost of medications saved was US$4596.
CONCLUSIONS: Nearly half (43.9%) of low-risk OH eyes in this setting could safely reduce medications over 1 year, realising substantial savings.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Ocular comorbidities among cataract-operated patients in rural China: the caring is hip Study of Cataract Outcomes and Uptake of Services (SCOUTS), report No. 3.

PURPOSE: To determine the prevalence and impact on vision and visual function of ocular comorbidities in a rural Chinese cataract surgical program, and to devise strategies to reduce their associated burden. DESIGN: Cross-sectional cohort study. PARTICIPANTS: Persons undergoing cataract surgery by one of two recently trained local surgeons at a government-run village-level hospital in rural Guangdong between August 8 and December 31, 2005. INTERVENTIONS: Eligible subjects were invited to return for a comprehensive ocular examination and visual function interview 10 to 14 months after surgery. Prevalent ocular comorbid conditions were identified. MAIN OUTCOME MEASURES: Presenting and best-corrected vision, visual function, and treatability of the comorbidity. RESULTS: Of 313 persons operated within the study window, 242 (77%) could be contacted by telephone; study examinations and interviews were performed on 176 (74%). Examined subjects had a mean age of 69.4+/-10.5 years, 116 (66%) were female, and 149 (85%) had been blind (presenting vision < or = 6/60) in the operative eye before surgery. Among unoperated eyes, 89 of 109 (81.7%) had > or =1 ocular comorbidities, whereas for operated eyes the corresponding proportion was 72 of 211 (34.1%). The leading comorbidity among operated eyes was refractive error (43/72 [59.7%]), followed by glaucoma/glaucoma suspect (14/72 [19.4%]), whereas for unoperated eyes, it was cataract (80/92 [87.0%]), followed by refractive error (12/92 [13.0%]). Among operated eyes with comorbidities, 90.3% (65/72) had > or =1 comorbidities that were treatable. In separate models adjusting for age and gender, persons with > or =1 comorbidities in the operated eye had significantly worse presenting vision (P<0.001) than those without such findings, but visual function (P = 0.197) and satisfaction with surgery (P = 0.796) were unassociated with comorbidities. CONCLUSIONS: Ocular comorbidities are highly prevalent among persons undergoing cataract surgery in this rural Asian setting, and their presence is significantly associated with poorer visual outcomes. The fact that the great majority of comorbidities encountered in this program are treatable suggests that strategies to reduce their impact can be successful.

Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure.

PURPOSE: To estimate the relationships between ocular parameters and tonometrically measured intraocular pressure (IOP), to determine the influence of ocular parameters on different instrument measurements of IOP, and to evaluate the association of ocular parameters with a parameter called hysteresis. METHODS: Patients presenting at a glaucoma clinic were recruited for this study. Subjects underwent IOP measurement with the Goldmann applanation tonometer (GAT), the TonoPen, and the Reichert Ocular Response Analyzer (ORA), and also measurements of central corneal thickness (CCT), axial length, corneal curvature, corneal astigmatism, central visual acuity, and refractive error. Chart information was reviewed to determine glaucoma treatment history. The ORA instrument provided a measurement called corneal hysteresis. The association between measured IOP and the other ocular characteristics was estimated using generalized estimating equations. RESULTS: Among 230 patients, IOP measurements from the TonoPen read lowest, and ORA read highest, and GAT measurements were closest to the mean IOP of the 3 instruments. In a multiple regression model adjusting for age, sex, race, and other ocular characteristics, a 10 microm increase in CCT was associated with an increase of 0.79 mm Hg measured IOP in untreated eyes (P<0.0001). Of the 3 tonometers, GAT was the least affected by CCT (0.66 mm Hg/10 mum, P<0.0001). Hysteresis was significantly correlated with CCT with a modest correlation coefficient (r=0.20, P<0.0007). CONCLUSIONS: Among parameters related to measured IOP, features in addition to CCT, such as hysteresis and corneal curvature, may also be important. Tonometric instruments seem to be affected differently by various physiologic characteristics.

Effectiveness of diode laser trans-scleral cyclophotocoagulation in patients following silicone oil-induced ocular hypertension in Chinese eyes.

We evaluated the effectiveness of diode laser trans-scleral cyclophotocoagulation (TSCPC) on intraocular pressure (IOP) in nine patients having raised IOP following use of silicone oil (SO) for retinal detachment (RD) surgery in a retrospective observational case series. Diode laser TSCPC was applied at a power setting of 1.75 to 2.5 watts, for two sec with a maximum of 30 applications. The patients were followed up for 40 to 312 weeks. The mean pre-laser IOP was 32.06 mm Hg (SD 7.32). The mean post-laser IOP at one month, three months and six months was 17.89 mm Hg (SD 8.23), 21.89 mm Hg (SD 8.16) and 21.67 mm Hg (SD 7.55) respectively. The final IOP (at the last follow-up) was 19.56 mm Hg (SD 7.85) (P=0.021). Seven of them had undergone SO removal. In our observation, effectiveness of TSCPC in long-term control of SO-induced ocular hypertension was limited as compared to short-term control of IOP.

Comparison of anterior ocular biometry between optical low-coherence reflectometry and anterior segment optical coherence tomography in an adult Chinese population.

PURPOSE: To evaluate the agreement between optical low-coherence reflectometry (OLCR) and anterior segment optical coherence tomography (AS-OCT) for biometry of the anterior segment. SETTING: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Evaluation of diagnostic technology. METHODS: A series of OLCR (Lenstar LS 900) and AS-OCT measurements of the anterior segment were taken for consecutive subjects aged 35 years and older in a population-based study. The differences and correlations between the 2 methods of ocular biometry were assessed. Agreement was calculated as the 95% limits of agreement (LoA). RESULTS: The mean age of the 776 subjects was 55.2 years ± 12.0 (SD); 54.6% were women. The mean central corneal thickness (CCT) was smaller with OLCR than with AS-OCT (537.84 ± 31.46 μm versus 559.39 ± 32.02 μm) as was anterior chamber depth (ACD) (2.60 ± 0.37 mm versus 2.72 ± 0.37 mm) and anterior chamber width (ACW) (11.76 ± 0.47 mm versus 12.04 ± 0.55 mm) (all P<.001). The 95% LoA between the 2 instruments were -44.80 to 1.71 μm for CCT, -0.17 to -0.06 mm for ACD, and -1.28 to 0.72 mm for ACW. CONCLUSION: Optical low-coherence reflectometry and AS-OCT yielded potentially interchangeable ACD measurements, while the CCT and ACW measurements acquired by the 2 devices showed clinically significant differences.

Monitoring ocular hypertension, how much and how often? A cost-effectiveness perspective

OBJECTIVE: To assess the efficiency of alternative monitoring services for people with ocular hypertension (OHT), a glaucoma risk factor.

DESIGN: Discrete event simulation model comparing five alternative care pathways: treatment at OHT diagnosis with minimal monitoring; biennial monitoring (primary and secondary care) with treatment if baseline predicted 5-year glaucoma risk is ≥6%; monitoring and treatment aligned to National Institute for Health and Care Excellence (NICE) glaucoma guidance (conservative and intensive).

SETTING: UK health services perspective.

PARTICIPANTS: Simulated cohort of 10 000 adults with OHT (mean intraocular pressure (IOP) 24.9 mm Hg (SD 2.4).

MAIN OUTCOME MEASURES: Costs, glaucoma detected, quality-adjusted life years (QALYs).

RESULTS: Treating at diagnosis was the least costly and least effective in avoiding glaucoma and progression. Intensive monitoring following NICE guidance was the most costly and effective. However, considering a wider cost-utility perspective, biennial monitoring was less costly and provided more QALYs than NICE pathways, but was unlikely to be cost-effective compared with treating at diagnosis (£86 717 per additional QALY gained). The findings were robust to risk thresholds for initiating monitoring but were sensitive to treatment threshold, National Health Service costs and treatment adherence.

CONCLUSIONS: For confirmed OHT, glaucoma monitoring more frequently than every 2 years is unlikely to be efficient. Primary treatment and minimal monitoring (assessing treatment responsiveness (IOP)) could be considered; however, further data to refine glaucoma risk prediction models and value patient preferences for treatment are needed. Consideration to innovative and affordable service redesign focused on treatment responsiveness rather than more glaucoma testing is recommended.

SHORT-TERM EFFECTS OF SALINITY ON SOME PHYSIOLOGICAL PARAMETERS OF YOUNG OLIVE TREES OF ARBEQUINA, COBRANÇOSA AND GALEGA VARIETIES

SHORT-TERM EFFECTS OF SALINITY ON SOME PHYSIOLOGICAL PARAMETERS OF YOUNG OLIVE TREES OF ARBEQUINA, COBRANÇOSA AND GALEGA VARIETIES Ana Elisa Rato1,4, Renato Coelho1, Margarida Vaz1, Teresa Carola2, Dália Barbosa2, Nádia Silva1, José dos Santos2, Lourenço Machado2, João Godinho2, Luzia Ruas2, Margarida Barradas2, Hernani Pereira2, Sara Porfírio4 1 ICAAM, Universidade de Évora, Apartado 94, 7002-554 Évora, Portugal 2 Master students, Universidade de Évora, Apartado 94, 7002-554 Évora, Portugal 3 Ph.D. student, Universidade de Évora, Apartado 94, 7002-554 Évora, Portugal 4 aerato@uevora.pt Due to the desertification in some regions, the interest in plant’s tolerance to salinity has been increasing, as this response is determining for plant survival in stress conditions. This work reports the investigation of tolerance to salt in two year-old olive trees (Olea europaea L.) of three varieties, Arbequina, Cobrançosa and Galega vulgar. Plants were grown in 10 L plastic pots containing approximately 9 Kg of a sandy granitic soil, on a greenhouse. For 3 months (from the beginning of February to the end of April 2012), they were subjected to three levels of salinity in the irrigation water, 0 mM, 80 mM and 200 mM NaCl (6 plants per salinity level in a total of 18 plants of each variety),. Stomatal conductance (gs) and relative leaf chlorophyll content were assessed on each plant in February, March and April. Mid-day leaf water potential () and soil salinity were measured at the end of the experiment (April). On average, concerning all treatments and dates of determination, stomatal conductance of Arbequina and Galega vulgar was quite similar, around 40 mmol m-2 s-1, but Cobrançosa had a value of gs 36% higher, almost 50% higher (61 mmol m-2 s-1) when compared with the controls (0 mM salt) of the other two varieties. In percentage of controls, there was little difference in gs between varieties and between salinities during February and March. In contrast, in April, after about 90 days of exposure to salt, there was a clear decrease in gs with salt irrigation, proportional to salt concentration. Compared with controls, plants irrigated with 200 mM salt showed around 80% (Arbequina) or 85% (Cobrançosa and Galega vulgar) decrease in gs. Chlorophyll content of leaves showed less than 5% difference between varieties on the average of all treatments and dates of determination. During the course of this experiment, the salinity levels used did not show any relevant effect on chlorophyll content. Overall, at the end of the experimental period (April), leaf water potential () at midday was significantly higher in Cobrançosa (-1,4 MPa) than in Galega vulgar (-1,7 MPa) or Arbequina (-1,8 MPa), and salt decreased  of control plants (-1,25 MPa) by an average 30% (with 80 mM) and 65% (with 200 mM). At the end of the experiment, salinity in the soil irrigated with 0 mM, 80 mM or 200 mM NaCl was, on average of all varieties, 0,2 mS, 1,0 mS or 2,0 mS, respectively. Soil salinity was quite similar in Arbequina and Galega vulgar but about 35% lower in the pots of Cobrançosa, on average of all salt-irrigation levels. Plants of Cobrançosa had higher stomatal conductance, however they showed higher water potential and lower salinity in the soil. These apparently contradictory results seem to suggest that Cobrançosa responds to salt differently from the other two varieties. This issue needs further investigation.

Novel critical phenomena in optimization driven processes on networks

The work presented in this Ph.D thesis was developed in the context of complex network theory, from a statistical physics standpoint. We examine two distinct problems in this research field, taking a special interest in their respective critical properties. In both cases, the emergence of criticality is driven by a local optimization dynamics. Firstly, a recently introduced class of percolation problems that attracted a significant amount of attention from the scientific community, and was quickly followed up by an abundance of other works. Percolation transitions were believed to be continuous, until, recently, an 'explosive' percolation problem was reported to undergo a discontinuous transition, in [93]. The system's evolution is driven by a metropolis-like algorithm, apparently producing a discontinuous jump on the giant component's size at the percolation threshold. This finding was subsequently supported by number of other experimental studies [96, 97, 98, 99, 100, 101]. However, in [1] we have proved that the explosive percolation transition is actually continuous. The discontinuity which was observed in the evolution of the giant component's relative size is explained by the unusual smallness of the corresponding critical exponent, combined with the finiteness of the systems considered in experiments. Therefore, the size of the jump vanishes as the system's size goes to infinity. Additionally, we provide the complete theoretical description of the critical properties for a generalized version of the explosive percolation model [2], as well as a method [3] for a precise calculation of percolation's critical properties from numerical data (useful when exact results are not available). Secondly, we study a network flow optimization model, where the dynamics consists of consecutive mergings and splittings of currents flowing in the network. The current conservation constraint does not impose any particular criterion for the split of current among channels outgoing nodes, allowing us to introduce an asymmetrical rule, observed in several real systems. We solved analytically the dynamic equations describing this model in the high and low current regimes. The solutions found are compared with numerical results, for the two regimes, showing an excellent agreement. Surprisingly, in the low current regime, this model exhibits some features usually associated with continuous phase transitions.

Phase transitions and nonlinear phenomena in neuronal network models

Communication and cooperation between billions of neurons underlie the power of the brain. How do complex functions of the brain arise from its cellular constituents? How do groups of neurons self-organize into patterns of activity? These are crucial questions in neuroscience. In order to answer them, it is necessary to have solid theoretical understanding of how single neurons communicate at the microscopic level, and how cooperative activity emerges. In this thesis we aim to understand how complex collective phenomena can arise in a simple model of neuronal networks. We use a model with balanced excitation and inhibition and complex network architecture, and we develop analytical and numerical methods for describing its neuronal dynamics. We study how interaction between neurons generates various collective phenomena, such as spontaneous appearance of network oscillations and seizures, and early warnings of these transitions in neuronal networks. Within our model, we show that phase transitions separate various dynamical regimes, and we investigate the corresponding bifurcations and critical phenomena. It permits us to suggest a qualitative explanation of the Berger effect, and to investigate phenomena such as avalanches, band-pass filter, and stochastic resonance. The role of modular structure in the detection of weak signals is also discussed. Moreover, we find nonlinear excitations that can describe paroxysmal spikes observed in electroencephalograms from epileptic brains. It allows us to propose a method to predict epileptic seizures. Memory and learning are key functions of the brain. There are evidences that these processes result from dynamical changes in the structure of the brain. At the microscopic level, synaptic connections are plastic and are modified according to the dynamics of neurons. Thus, we generalize our cortical model to take into account synaptic plasticity and we show that the repertoire of dynamical regimes becomes richer. In particular, we find mixed-mode oscillations and a chaotic regime in neuronal network dynamics.

Chronic symptoms after vestibular neuritis and the high velocity vestibulo-ocular reflex

Hypothesis: As the anterior and posterior semicircular canals are vital to the regulation of gaze stability, particularly during locomotion or vehicular travel, we tested whether the high velocity vestibulo‐ocular reflex (VOR) of the three ipsilesional semicircular canals elicited by the modified Head Impulse Test would correlate with subjective dizziness or vertigo scores after vestibular neuritis (VN). Background: Recovery following acute VN varies with around half reporting persistent symptoms long after the acute episode. However, an unanswered question is whether chronic symptoms are associated with impairment of the high velocity VOR of the anterior or posterior canals. Methods: Twenty patients who had experienced an acute episode of VN at least three months earlier were included in this study. Participants were assessed with the video head impulse test (vHIT) of all six canals, bithermal caloric irrigation, the Dizziness Handicap Inventory (DHI) and the Vertigo Symptoms Scale short‐form (VSS). Results: Of these 20 patients, 12 felt that they had recovered from the initial episode whereas 8 did not and reported elevated DHI and VSS scores. However, we found no correlation between DHI or VSS scores and the ipsilesional single or combined vHIT gain, vHIT gain asymmetry or caloric paresis. The high velocity VOR was not different between patients who felt they had recovered and patients who felt they had not. Conclusions: Our findings suggest that chronic symptoms of dizziness following VN are not associated with the high velocity VOR of the single or combined ipsilesional horizontal, anterior or posterior semicircular canals.

Effects of Prochlorperazine on Normal Vestibular Ocular and Perceptual Responses: A Randomised, Double-Blind, Crossover, Placebo-Controlled Study

Background: The present study investigated whether prochlorperazine affects vestibular-ocular reflex (VOR) and vestibulo-perceptual function. Methods: We studied 12 healthy naïve subjects 3 hours after a single dose of oral prochlorperazine 5mg in a randomised, placebo-controlled, double-blind, cross-over study in healthy young subjects. Two rotational tests in yaw were used: 1) a Threshold task investigating perceptual motion detection and nystagmic thresholds (acceleration steps of 0.5deg/s/s) and 2) Suprathreshold responses to velocity steps of 90deg/s in which vestibulo-ocular (VO) and vestibulo-perceptual (VP) time constants of decay, as well as VOR gain, were measured. Results: Prochlorperazine had no effect upon any measure of nystagmic or perceptual vestibular function compared to placebo. This lack of effects on vestibular-mediated motion perception suggests that the drug is likely to act more as an antiemetic than as an anti-vertiginous agent.

Development and Progress as Historical Phenomena in Tanzania: “Maendeleo? We Had That in the Past”

Academic discussions of development continue to grow, yet critical engagements with communities affected by development interventions remain limited. Drawing from life history interviews conducted in southern Tanzania, this article details the varied experiences of development interventions among older people and how these affect broader understandings of progress. Many juxtapose their negative views of ujamaa villagization with more positive recollections of previous interventions (especially the Groundnut Scheme), which are infused with what is described here as “development nostalgia.” Perceptions of the past clearly inform the social, political, and economic aspirations forwarded today, with the richness of the constructed narratives adding further nuance to existing depictions of Tanzanian historiography.

Characterisation of physiological conditions and evaluation of well-being in two species of bivalve molluscs (Ruditapes philippinarum and Chamelea gallina) intensively exploited in coastal and lagoon areas of the Northern Adriatic Sea (Italy)

Tese de Doutoramento, Ecologia, Especialidade de Ecofisiologia, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2007

Development of non-viral vectors for gene therapy for pathologies of the retina

Tese de doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Kyotorphin derived peptides in the relationship between analgesia and alzheimer’s disease

Tese de doutoramento, Ciências Biomédicas (Bioquímica Médica), Universidade de Lisboa, Faculdade de Medicina, 2014