Miguel Raimundo

Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study

Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

Robust single trial identification of conscious percepts triggered by sensory events of variable saliency.

The neural correlates of visual awareness are elusive because of its fleeting nature. Here we have addressed this issue by using single trial statistical “brain reading” of neurophysiological event related (ERP) signatures of conscious perception of visual attributes with different levels of saliency. Behavioral reports were taken at every trial in 4 experiments addressing conscious access to color, luminance, and local phase offset cues. We found that single trial neurophysiological signatures of target presence can be observed around 300 ms at central parietal sites. Such signatures are significantly related with conscious perception, and their probability is related to sensory saliency levels. These findings identify a general neural correlate of conscious perception at the single trial level, since conscious perception can be decoded as such independently of stimulus salience and fluctuations of threshold levels. This approach can be generalized to successfully detect target presence in other individuals.

Adherence to a Mediterranean diet and its association with age-related macular degeneration. The Coimbra Eye Study–Report 4

OBJECTIVESnThis study aimed to characterize the association of lifestyle and nutritional risk profiles with age-related macular degeneration (AMD) in two subpopulations with differing AMD prevalence.nnnMETHODSnThis case-control study (nu2009=u20091992) included 768 patients with AMD and 1224 age- and sex-matched participants without AMD with a single visit at a primary health care unit. Enrolled participants completed a validated lifestyle and food frequency questionnaire. A score to measure adherence to the Mediterranean diet (mediSCORE; Range, 0-9) was constructed from individual food intakes, which were further analyzed by conversion to nutrient consumption.nnnRESULTSnHigher adherence to the Mediterranean diet (mediSCORE ≥6) was significantly associated with no AMD (odds ratio [OR]u2009=u20090.73; Pu2009=u20090.009). The subpopulation with lower AMD prevalence presented significantly higher adherence to the Mediterranean diet in relation to all individual food groups that comprised the mediSCORE (Pu2009<u20090.014) with the exception of cereals. Food group analysis showed significant associations between the increased consumption of vegetables (ORu2009=u20090.63; Pu2009<u20090.001) and fruit and nuts (ORu2009=u20090.78; Pu2009=u20090.010) with no AMD. Nutrient analysis revealed that an increased ingestion of water, fibers, total fat, monounsaturated and polyunsaturated fatty acids, linoleic acid, vitamins A and C, carotene, alpha-tocopherol, folate, magnesium, iron, and zinc were significantly associated with no AMD (Pu2009<u20090.0013). Finally, regular physical activity was associated with no AMD (Pu2009=u20090.003).nnnCONCLUSIONSnHigh adherence to a Mediterranean diet and regular physical activity seem to be protective factors for AMD in a Portuguese population. The effect of the diet is likely driven by the increased consumption of vegetables, fruits, and nuts.

The Portuguese Experience with Ocriplasmin in Clinical Practice

Aim: Evaluate the real-life experience with ocriplasmin on vitreomacular traction (VMT) release and full-thickness macular hole (FTMH) closure in Portugal. Methods: Multicentric, retrospective study of 83 eyes of 78 patients who were treated with intravitreal ocriplasmin for VMT with and without FTMH. Primary outcomes were VMT release and FTMH closure. Secondary outcomes included visual acuity changes and structural features on spectral-domain ocular coherence tomography. Results: VMT resolved in 47 of the 83 eyes (56.6%) and 6 of the 12 FTMH were closed (50.0%). Mean best-corrected visual acuity (BCVA) improved from 65.1 at baseline to 70.8 ETDRS letters at the end of follow-up (p < 0.0001) with a mean follow-up of 138.8 days. Improvement in BCVA was significantly better in eyes with VMT release (p = 0.021). Approximately 73% of patients had normal ellipsoid zone integrity at the end of follow-up, 87% had no neurosensorial detachment and 40% had no intra- or subretinal fluid. Conclusion: VMT release and FTMH closure were achieved in more than half of the treated eyes and were correlated with significant BCVA improvements and favorable baseline characteristics. In fact, if a careful patient selection is carried out, VMT resolution with ocriplasmin can be optimized, tailoring the best approach to each patient.

A New Approach to Assess Early Progressive Loss Across Multiple Visual Channels In the Natural History of Glaucoma.

Purpose:We aimed to evaluate the ability of new psychophysical discrimination tests, based on readily available hardware, to probe motion, achromatic, and chromatic contrast sensitivity, across the natural history of glaucoma. We assessed the sensitivity of these tests to detect functional damage at ocular hypertension stage, using receiver operating characteristic analysis. We also explored whether eccentricity-related patterns of damage change with disease progression. Patients and Methods:We studied a cohort of 43 participants, who were divided between different groups: ocular hypertension (n=16 eyes), glaucoma suspects (n=15), and primary open-angle glaucoma (n=12). These patients were compared with an age-matched control group (n=15 eyes). We tested distinct subsets of retinal ganglion cell populations using 3 novel 2-alternative forced choice psychophysical discrimination tests (independent variables: motion, achromatic, and chromatic L, M, and S-cone contrasts) between 2 separated peripheral, small moving single dots at 4 distinct meridians. Notably these tests were implemented in relatively standard hardware. Results:All tests showed significant correlation with disease progression (mean &rgr;±SD=0.708±0.075; P<0.0001) and had sufficient power to discriminate glaucoma subgroups. Most tests using this design had large sensitivity (above 90% for 80% specificity) to detect functional damage at the ocular hypertensive stage. Disease-related eccentricity patterns of damage were also found, matching the expected pattern of progression. Conclusions:Our new psychophysical discrimination tests are capable of probing disease progression and to detect functional damage at ocular hypertension stage. It is therefore possible to customize psychophysical test software to detect early changes and monitor disease progression, including progressive loss of functional reserve, using relatively simple hardware.

Influence of the Vitreoretinal Interface on the Treatment with Anti-VEGF for Exudative Age-Related Macular Degeneration

Purpose: To investigate the influence of the vitreoretinal interface on the outcomes of different ranibizumab regimens for exudative age-related macular degeneration. Methods: We conducted a retrospective subanalysis of 2 prospective clinical trials. Patients were treated with ranibizumab for 12 months according to 3 different regimens: pro-re-nata (PRN), treat and extend (T&E), and monthly. Vitreoretinal interface was assessed for absence (group ON) or presence (group OFF) of posterior vitreous detachment (PVD). Results: We included 64 eyes from 64 patients. Visual improvement was poorer for group ON (0.3 ± 10.7 letters) than for group OFF (9.2 ± 13.3; p = 0.007). A significant difference in letters of improvement between groups was observed in the PRN cohort (ON: –5.0 ± 12.9; OFF: 11.4 ± 11.9; p = 0.003), but not in the cohorts with monthly (ON: 5.7 ± 7.8; OFF: 7.9 ± 15.2; p = 0.735) or T&E (ON: 4.3 ± 4.3; OFF: 7.8 ± 11.1; p = 0.424) treatment. Conclusion: The negative impact of absence of PVD is regimen dependent, with monthly dosing providing similar outcomes to PVD patients. In the absence of PVD (group ON), PRN should be avoided, and T&E might be an alternative.

Epiretinal Proliferations Associated with Lamellar Macular Holes: Clinical and Surgical Implications

Objectives: To describe the prevalence of lamellar hole-associated epiretinal proliferation (LHEP) and to correlate this finding with lamellar macular hole (LMH) morphology and prognosis after a surgical or conservative approach. Methods: This is a retrospective multicenter case series comprising consecutive LMH patients followed for ≥6 months. Serial spectral-domain optical coherence tomographies were evaluated for the presence of epiretinal membrane (ERM) and LHEP, diameter of the LMH aperture, base, and floor thickness. Pars plana vitrectomy with ERM and internal limiting membrane peeling was performed in the surgical cases. Results: A total of 62 eyes from 57 consecutive patients were included. Mean follow-up time was 27.1 ± 19.8 months. LHEP was observed in 33 (53.2%) eyes. Patients with LMH and LHEP presented a larger external diameter (p = 0.001) and thinner floors (p = 0.018). Twenty-seven (81.8%) of the patients with LMH and LHEP presented a degenerative intraretinal cavitation, compared to 23.3% in the non-LHEP group (p = 0.001). No differences were observed in visual performance or closure rate between the 2 groups after surgery or in the subset of patients followed conservatively. Conclusions: LHEP was correlated with the anatomical conformation of the LMH, yielding thinner floors and larger external diameters. However, it did not correlate with the anatomical or functional results, both in the patients who underwent surgery and in those managed conservatively.

Optical coherence tomography angiography characterization of acute and late stage Purtscher retinopathy

Purpose: To report a case of Purtscher retinopathy imaged with optical coherence tomography angiography. Methods: Case-report. Left eye fundoscopic examination in a 21-year old male after a road traffic accident with chest compression revealed multiple peri-papillary cotton-wool spots and intra- and pre-retinal hemorrhages. A diagnosis of Purtscher retinopathy was assumed. Results: In both the superficial and deep retinal plexuses, acute stage optical coherence tomography angiography identified multiple irregular areas of capillary non-perfusion that extended beyond the clinically visible peri-papillary cotton-wool spots. At 5-month follow-up, despite the clearing of visible cotton-wool spots, there were still permanent areas of irregular capillary non-perfusion and inner retina atrophy. These sequelae, along with a decrease in the peri-papillary retinal nerve fiber layer thickness, were consistent with a suboptimal visual outcome and a dense inferior arcuate scotoma. Conclusion: Baseline and follow-up optical coherence tomography angiography was able to detect, quantify, and map focal microvascular abnormalities at the level of the superficial and deep inner retinal vascular plexuses. These lesions were consistent with late stage structural and functional sequelae, conferring them prognostic value.

Bilateral giant macular holes: A rare manifestation of Alport syndrome

Purpose: Alport syndrome is a rare condition characterized by the clinical triad of nephritic syndrome, sensorineural deafness, and ophthalmological alterations. Herein, we present a rare case of a patient diagnosed with Alport syndrome and bilateral giant macular holes. Case description: A 40-year-old woman with a previously unreported mutation in the COL4A4 gene suggestive of autosomal-recessive Alport syndrome presented at our department. The patient exhibited bilateral full-thickness macular holes measuring >1500u2009µm at their smallest diameters. The very large dimensions of both macular holes were indicative of a bad prognosis regarding hole closure, and a conservative approach was adopted. The patient was maintained on renal substitution therapy, and genetic counseling was offered to other family members. Conclusion: Ophthalmological findings associated to Alport syndrome commonly include anterior lenticonus and dot-and-fleck retinopathy, although giant macular holes can also be associated with this condition. A multidisciplinary approach is crucial in the management of these patients, as Alport syndrome is an inherited systemic basement membrane disease.

The National Student Survey: validation in Portuguese medical students

Abstract The UK National Student Survey (NSS) is a sound and widely used instrument for assessing students’ academic experiences. We aimed to translate the NSS for Portuguese students and to validate the instrument in a sample of medical undergraduates. The research team translated and adapted the NSS for Portuguese students (NSS-P). The survey was administered on an online platform to 1,256 final-year students at eight Portuguese medical schools. A total of 329 medical students (69.9% female) replied to the NSS-P, a response rate of 26.2%. Confirmatory factor analysis showed that the original six-factor structure had an adequate fit to the data. Adequate internal consistency was observed for all the subscales. Medium to large correlations were found among all the subscale scores and between the subscale scores and the students’ overall satisfaction. Multiple regression showed that the scores on the Teaching, Organization and Management and Personal Development subscales significantly predicted the students’ overall satisfaction. Approximately 64% of the students reported being satisfied with the quality of their courses. Significant differences among the medical schools in their NSS-P scores were found. The NSS-P is a valid and reliable measure for assessing medical students’ perceptions of academic quality.