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- Central and peripheral involvement of the retina in the initial stages of diabetic retinophatyPublication . Santos, Ana Rita; Almeida, Ana Catarina; Rocha, Ana Cláudia; Reste-Ferreira, Débora; Marques, Inês Pereira; Martinho, António Cunha-Vaz; Mendes, Luís; Santos, Torcato; Lewis, Warren; Cunha-Vaz, José; Santos, Ana RitaTo determine the degree of central microvascular closure using optical coherence tomography angiography in eyes of patients with type 2 diabetes with visible lesions only in the central retina or only in the periphery. Cross-sectional study. All 127 eyes underwent ultra-widefield fundus photography 200° examinations with OPTOS California (Optos, Dunfermline, United Kingdom) and Cirrus Angioplex optical coherence tomography angiography 3 × 3 mm acquisitions (ZEISS, Dublin, CA). Twenty-five eyes showed visible lesions only in the central retina, 57 only in the peripheral retina, and 45 presented visible lesions in entire retina. The group with visible lesions only in the periphery showed definite closure in the superficial capillary plexus in 49% of the eyes, whereas the group with visible lesions only in the central seven-early treatment diabetic retinopathy study fields area showed a definite closure in 64%. Central capillary closure is already present in the initial stages of diabetic retinopathy even when lesions are only visible in the peripheral retina. Capillary closure in the superficial capillary plexus is three times more frequent than in the deep capillary plexus, demonstrating earlier closure of the superficial capillary plexus. Eyes with visible lesions only in the periphery show a milder form of retinopathy.
- Retinal neurodegeneration in eyes with NPDR risk phenotypes: A two-year longitudinal studyPublication . Reste-Ferreira, Débora; Santos, Ana Rita; Marques, Inês Pereira; Santos, Torcato; Ribeiro, Maria Luísa; Mendes, Luís; Santos, Ana Rita; Lobo, Conceição; Cunha-Vaz, JoséDiabetic retinopathy (DR) is both a microangiopathy and a neurodegenerative disease. However, the connections between both changes are not well known. To characterise the longitudinal retinal ganglion cell layer + inner plexiform layer (GCL + IPL) changes and their association with microvascular changes in type-2 diabetes (T2D) patients with nonproliferative diabetic retinopathy (NPDR). This two-year prospective study (CORDIS, NCT03696810) included 122 T2D individuals with NPDR identified as risk phenotypes B and C, which present a more rapid progression. Phenotype C was identified by decreased VD ≥ 2SD in healthy controls, and phenotype B, identified by subclinical macular oedema with only minimal vascular closure. The GCL + IPL thickness, vessel density, perfusion density and area of intercapillary spaces (AIS) were assessed by optical coherence tomography (OCT) and OCT angiography (OCTA). Linear mixed effects models were employed to evaluate the retinal GCL + IPL progression and its associations. Regarding GCL + IPL thickness, T2D individuals presented on average 80.1 ± 7.49 μm, statistically significantly lower than the healthy control group, 82.5 ± 5.71 (p = 0.022), with only phenotype C differing significantly from controls (p = 0.006). GCL + IPL thickness steadily decreased during the two-year period in both risk phenotypes, with an annual decline rate of −0.372 μm/year (p < 0.001). Indeed, phenotype C showed a higher rate of progression (−0.459 μm/year, p < 0.001) when compared to phenotype B (−0.296 μm/year, p = 0.036). Eyes with ETDRS grade 20 showed GCL + IPL thickness values comparable to those of healthy control group (83.3 ± 5.80 and 82.7 ± 5.50 μm, respectively, p = 0.880), whereas there was a progressive decrease in GCL + IPL thickness in ETDRS grades 35 and 43–47 associated with the increase in severity of the retinopathy (−0.276 μm/year, p = 0.004; −0.585 μm/year, p = 0.013, respectively). Furthermore, the study showed statistically significant associations between the progressive thinning of GCL + IPL and the progressive increase in retinal capillary non-perfusion, with particular relevance for AIS (p < 0.001). Our findings showed that, in eyes with NPDR and at risk for progression, retinal neurodegeneration occurs at different rates in different risk phenotypes, and it is associated with retinal microvascular non-perfusion.
- Progression of capillary hypoperfusion in advanced stages of nonproliferative diabetic Retinopathy: 6-month Analysis of RICHARD studyPublication . Marques, Inês Pereira; Reste-Ferreira, Débora; Santos, Torcato; Mendes, Luís; Yamaguchi, Taffeta Ching Ning; Santos, Ana Rita; Pearce, Elizabeth; Cunha-Vaz, JoséTo evaluate the 6-month progression of retinal capillary perfusion in eyes with advanced stages of nonproliferative diabetic retinopathy (NPDR). Design: RICHARD (NCT05112445), 2-year prospective longitudinal study. Participants: Sixty eyes with Diabetic Retinopathy Severity Scale (DRSS) levels 43, 47, and 53 from 60 patients with type 2 diabetes. Fifty-one patients completed the 6-month evaluation. Eyes were evaluated on Optos California (Optos plc) ultrawidefield fundus fluorescein angiography (UWF-FFA), swept-source OCT angiography (SS-OCTA) (PLEX Elite 9000, ZEISS) and spectral-domain OCTA (SD-OCTA) (CIRRUS HD-OCT 5000 Angioplex, ZEISS). DRSS classification was performed based on 7-field color fundus photographs (CFPs) complemented with Optos California UWF-fundus imaging. Main Outcome Measures: Ischemic index was obtained from Optos. Vascular quantification metrics, namely foveal avascular zone, skeletonized vessel density (SVD), and perfusion density (PD) metrics, were acquired on OCTA in the superficial and deep capillary plexuses (SCP and DCP). Microaneurysm assessment was automatically performed based on CFP images using the RetmarkerDR (Retmarker SA, Meteda Group). Swept-source-OCTA metrics showed statistically significant differences between the advanced stages of NPDR. Differences between DRSS levels 47 and 53 were found at baseline in the inner ring (SVD, SCP: P¼0.005andDCP:P¼0.042andPD,SCP:P¼0.003)andouterring (SVD,SCP: P¼0.007andDCP:P¼0.030 and PD, SCP: P ¼ 0.020 and DCP: P ¼ 0.025). No significant differences were observed at baseline between DRSS levels 43 and 47. In SD-OCTA, the differences were similar but did not reach statistical significance. The total ischemic index showed an increase in association with diabetic retinopathy (DR) severity, but the differences between DRSS levels did not reach statistical significance. The number of microaneurysms also increased significantly with DR severity (P ¼ 0.033). Statistically significant 6-month progression was detected with SSOCTA in eyes with DRSS levels 47 and 53 but not in DRSS level 43. In eyes with DRSS level 53, 6-month progression was identified using a combination of metrics of capillary nonperfusion and microaneurysm counts. In a 6-month period, significant microvascular disease progression can be identified in eyes with DRSS levels 47 and 53 by performing OCTA examinations and microaneurysm counting using CFP.
- Patterns of progression of nonproliferative diabetic retinopathy using non-invasive imagingPublication . Marques, Inês Pereira; Ribeiro, Maria Luísa; Santos, Torcato; Reste-Ferreira, Débora; Mendes, Luís; Martinho, António Cunha-Vaz; Santos, Ana Rita; Figueira, João; Lobo, Conceição; Cunha-Vaz, JoséTo identify progression of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes by combining optical coherence tomography angiography (OCTA) metrics and color fundus photography (CFP) images. This study was a post hoc analysis of a prospective longitudinal cohort study (CORDIS, NCT03696810) with 2-year duration. This study enrolled 122 eyes. Ophthalmological examinations included OCTA and CFP. OCTA metrics included skeletonized vessel density (SVD) and perfusion density (PD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Microaneurysm turnover analysis and Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment were performed on 7-field CFP. Eyes graded as ETDRS level 20 showed significant capillary nonperfusion predominantly in the inner ring area in the SCP (P < 0.001), whereas eyes graded as ETDRS level 35 and ETDRS levels 43 and 47 showed significant capillary nonperfusion in both the SCP and DCP in both inner and outer rings (P < 0.001). When evaluating rates of progression in capillary nonperfusion for the 2-year period of follow-up, changes were found predominantly in the DCP for SVD and PD and were better identified in the outer ring area. Microaneurysm turnover contributes to the characterization of NPDR progression by discriminating ETDRS level 35 from ETDRS levels 43 and 47 (P < 0.001), which could not be achieved using only OCTA metrics. Patterns of progression of NPDR can be identified combining OCTA examinations of the superficial and deep retinal capillary plexi of central retina and determination of microaneurysm turnover from fundus photographs. Our study reports results from a registered clinical trial that advances understanding of disease progression in NPDR.
- ETDRS grading with CLARUS ultra-widefield images shows agreement with 7-fields colour fundus photographyPublication . Santos, Ana Rita; Ghate, Sejal; Lopes, Marta; Rocha, Ana Cláudia; Santos, Torcato; Reste-Ferreira, Débora; Manivannan, Niranchana; Foote, Katharina; Cunha-Vaz, José; Santos, Ana RitaTo analyse and compare the grading of diabetic retinopathy (DR) severity level using standard 35° ETDRS 7-fields photography and CLARUS™ 500 ultra-widefield imaging system. A cross-sectional analysis of retinal images of patients with type 2 diabetes (n=160 eyes) was performed for this study. All patients underwent 7-fields colour fundus photography (CFP) at 35° on a standard Topcon TRC50DX® camera, and ultra-widefield (UWF) imaging at 200° on a CLARUS™ 500 (ZEISS, Dublin, CA, USA) by an automatic montage of two 133° images (nasal and temporal). 35° 7-fields photographs were graded by two graders, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). For CLARUS UWF images, a prototype 7-fields grid was applied using the CLARUS review software, and the same ETDRS grading procedures were performed inside that area only. Grading of DR severity level was compared between these two methods to evaluate the agreement between both imaging techniques. Images of 160 eyes from 83 diabetic patients were considered for analysis. According to the 35° ETDRS 7-fields images, 22 eyes were evaluated as DR severity level 10–20, 64 eyes were evaluated as DR level 35, 41 eyes level 43, 21 eyes level 47, 7 eyes level 53, and 5 eyes level 61. The same DR severity level was achieved with CLARUS 500 UWF images in 92 eyes (57%), showing a perfect agreement (k>0.80) with the 7-fields 35° technique. Fifty-seven eyes (36%) showed a higher DR level with CLARUS UWF images, mostly due to a better visualization of haemorrhages and a higher detection rate of intraretinal microvascular abnormalities (IRMA). Only 11 eyes (7%) showed a lower severity level with the CLARUS UWF system, due to the presence of artifacts or media opacities that precluded the correct evaluation of DR lesions. UWF CLARUS 500 device showed nearly perfect agreement with standard 35° 7-fields images in all ETDRS severity levels. Moreover, CLARUS images showed an increased ability to detect haemorrhages and IRMA helping with finer evaluation of lesions, thus demonstrating that a UWF photograph can be used to grade ETDRS severity level with a better visualization than the standard 7-fields images.
- Intraretinal microvascular abnormalities in eyes with advanced stages of nonproliferative diabetic Retinopathy: Comparison between UWF-FFA, CFP, and OCTA-The RICHARD studyPublication . Santos, Ana Rita; Lopes, Marta; Santos, Torcato; Reste‑Ferreira, Débora; Marques, Inês P.; Yamaguchi, Taffeta C. N.; Miranda, Telmo; Mendes, Luís; Martinho, António C. V.; Pearce, Liz; Cunha‑Vaz, JoséThis study aimed to evaluate intraretinal microvascular abnormalities (IRMA) in eyes with advanced nonproliferative diabetic retinopathy (NPDR) using multimodal approach in co-located areas focusing on central retina (up to 50°) and to look at possible correlations between IRMA and other structural changes, like ischemia and presence of microaneurysms. The RICHARD study (NCT05112445) included 60 eyes from 60 patients with type 2 diabetes with moderate-severe NPDR, diabetic retinopathy severity levels 43, 47, and 53 (DRSS). IRMA were defined as capillary tortuosity covering a minimum circular area of 300 µm (calculated to correspond to the Early Treatment Diabetic Retinopathy Study standard photo 8A) and were identified using multimodal imaging with distinct fields of view (FoV): color fundus photography (CFP) using a Topcon TRC-50DX camera (Topcon Medical Systems, Japan), Optos California ultra wide field fundus fluorescein angiography (UWF-FFA) (Optos plc, UK), and swept-source optical coherence tomography angiography (SS-OCTA) (PLEX® Elite 9000, ZEISS, USA). Different areas of the retina were examined: central macula (up to 20°) and posterior pole (between 20° and 50°). Multimodal imaging was used to identify IRMA in co-located areas (FoV < 50°) including UWF-FFA, CFP, and SS-OCTA. In eyes with DRSS levels 47 and 53, IRMA were identified in both areas of the retina, while in eyes with DRSS level 43, IRMA were detected only outside of the central macula (FoV > 20°). Our results show that when evaluating the presence of IRMA (FoV < 50°), UWF-FFA detected 203 IRMA, SS-OCTA detected 133 IRMA, and CFP detected 104 IRMA. Our results also show that the presence of IRMA was positively associated with presence of microaneurysms. dentification of IRMA in eyes with advanced NPDR is better achieved by UWF-FFA than CFP and SS-OCTA. A statistically significant correlation was found between the presence of IRMA and the increase in number of microaneurysms.
- Interventions based on biofeedback systems to improve workers’ psychological well-being, mental health and safety: a systematic literature reviewPublication . Ferreira, Simão; Rodrigues, Matilde A.; Mateus, Catarina; Rodrigues, Pedro Pereira; Rocha, Nuno Barbosa; Ferreira, Simão; Rodrigues, Matilde; Mateus, Catarina; Rocha, NunoIn modern, high-speed work settings, the significance of mental health disorders is increasingly acknowledged as a pressing health issue, with potential adverse consequences for organizations, including reduced productivity and increased absenteeism. Over the past few years, various mental health management solutions, such as biofeedback applications, have surfaced as promising avenues to improve employees' mental well-being. To gain deeper insights into the suitability and effectiveness of employing biofeedback-based mental health interventions in real-world workplace settings, given that most research has predominantly been conducted within controlled laboratory conditions. A systematic review was conducted to identify studies that used biofeedback interventions in workplace settings. The review focused on traditional biofeedback, mindfulness, app-directed interventions, immersive scenarios, and in-depth physiological data presentation. The review identified nine studies employing biofeedback interventions in the workplace. Breathing techniques showed great promise in decreasing stress and physiological parameters, especially when coupled with visual and/or auditory cues. Future research should focus on developing and implementing interventions to improve well-being and mental health in the workplace, with the goal of creating safer and healthier work environments and contributing to the sustainability of organizations.
- Angiografia por tomografia de coerência ótica na queratoplastia penetrantePublication . Aguiar, Catarina Pestana; Jesus, Jeniffer; Dias, Libânia; Gonçalves, Susana; João, Matias Maria; Miranda, Vítor; Ambrósio, João; Chibante-Pedro, João; Almeida, InêsA queratoplastia penetrante (QP) é um dos procedimentos cirúrgicos mais realizados na transplantação corneana mundialmente. A falência do enxerto e o risco de rejeição aumentam progressivamente com o aumento do número de quadrantes com neovascularização corneana (NVC). A angiografia por tomografia de coerência ótica (OCTA) é um exame não invasivo que tem sido largamente utilizado na visualização de anomalias vasculares da retina e algunsestudos demonstraram a sua potencial utilização no segmento anterior do olho. O objetivo deste estudo foi investigar o potencial da tecnologia da OCTA na aquisição de imagens e descrição quantitativa da NVC em olhos submetidos a QP. Estudo transversal, com 20 olhos de 18 doentes submetidos a QP pelo menos 5 anos antes e sem história de rejeição do transplante. A todos os olhos foi realizada uma fotografia do segmento anterior na lâmpada de fenda (LF) e uma aquisição de imagens en face, b-scans e c-scans da OCTA. A densidade vascular (DV) foi analisada na margem corneana inferior, nasal e temporal em todos os doentes. A medição da DV foi obtida após criação de imagens binárias com o software ImageJ, usando imagens da OCTA com 6 × 6 mm numa profundidade de 800 μm. A idade média dos doentes foi de 59 anos e a maioria foi submetido a QP por leucoma corneano, seguido de queratocone. A DV total média foi de 50,16% e foi mais alta no quadrante temporal e mais baixa no quadrante inferior. No entanto, não se verificou uma diferença estatisticamente significativa entre as 3 áreas analisadas (p=0,801) ou entre cada área e as duas restantes e não se verificou uma correlação entre as áreas. A OCTA foi capaz de identificar vasos anormais quando as fotografias na LF não os identificavam; a OCTA foi capaz de distinguir entre vasos de grande e pequeno calibre; a OCTA permitiu a investigação em diferentes planos corneanos. A OCTA poderá tornar-se um novo método para a monitorização de doenças corneanas e permitir o seguimento qualitativo e quantitativo de pacientes submetidos a QP, com a deteção precoce de NVC.
- Sensitivity of psychophysical, electrophysiological and structural tests for detection and progression monitoring in ocular hypertension and glaucomaPublication . Raimundo, Miguel; Mateus, Catarina; Faria, Pedro; Oliveiros, Bárbara; Cardoso, João; Silva, João Filipe; Pereira, José Moura; Castelo-Branco, MiguelTo characterize early visual impairment of patients in the glaucoma spectrum, using psychophysical, electrophysiological and structural methods. Cohort of 52 patients, 18 patients with ocular hypertension (HT), 15 glaucoma suspects (GS) and 19 with primary open-angle glaucoma (G), and 20 age-matched controls. Quantitative psychophysical methods were used to assess magno (FDT, Frequency Doubling Technology), parvo and koniocellular pathways (Cambridge Color Test), and RGC function was assessed by Pattern Electroretinogram. RGC axonal thickness was obtained using OCT. Reduced mean achromatic contrast sensitivity (p=0.0298) was found in patients with HT, as well as a reduced PERG N-95 wave amplitude (p=0.0499). Chromatic thresholds were significantly increased for protan, deutan and tritan axes (p<0.03) in these patients when compared to controls. At approximately 80% specificity, FDT showed only moderate sensitivity to detect early functional damage (superior nasal, 66% sensitivity). The pattern of disease progression decline is approximately linear for all tests, but more severe in OCT, RNFL thickness ( = 0.47). We found relative damage of magno, parvo and koniocellular retinocortical pathways beginning in ocular hypertension. FDT and CCT Protan performed well in detecting early damage in ocular hypertension, whereas longitudinal analysis using OCT for RFNL appeared to be the best to monitor the progression. The sensitivity of currently available tests is lower comparing with our previously reported novel psychophysical tools (sensitivity above 90% for 80% specificity). We believe early diagnosis in glaucoma is possible by exploiting visual pathways with a small degree of redundancy through high sensitivity functional tests.
- Analysis of choroidal macular thickness in early post-Covid-19 patientsPublication . Jesus, Jeniffer Domingues de; Soares, Raquel J.; Dias, Libânia; Ventura, Suzana M.; Pedro, João C.Corona Virus Disease 2019 (COVID-19) is considered a critical global health challenge. Several investigations have suggested vascular dysfunction caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, but regarding ophthalmic involvement, only few data are available. Our aim was to evaluate the choroidal involvement in post-COVID-19 patients. 40 eyes from 40 patients with previous SARS-CoV-2 infection and 40 eyes from 40 age matched controls were included. Choroidal measurements were made using Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) at 13 different locations: at central fovea and at intervals of 500μm to 1500μm away from the fovea in the temporal, nasal, superior and inferior regions. Post-COVID-19 patients showed a significant increase in choroidal thickness compared with the control group for all the regions analyzed (all p <0.01). In the Post-COVID-19 group, the choroid is thickest subfoveally and thinnest 1500μm nasal from fovea. In both groups, the superior and temporal macular choroid has been measured thicker than the inferior and nasal macular choroid, respectively. Our results cautiously suggest that post-COVID-19 patients showed an increase in choroidal thickness compared to control groups. This choroidal thickening may reflect the importance of vascular factors in the pathogenesis of SARS-CoV-2 infection. Keywords: Choroid; COVID-19; Hemodynamic Changes; Ocular Circulation; Retina; SARS-CoV-2