Corneal transplantation activity in Catalonia, Spain, from 2011 to 2018: evolution of indications and surgical techniques.

Purpose: To report corneal transplant activity carried out in Catalonia (Spain) and the evolving indications for keratoplasty over an 8-year period. Methods: Annual reports from the Catalan Transplant Organization, Spain, on corneal graft indications and techniques from 2011 to 2018 were reviewed. Results: A total of 9457 keratoplasties were performed in Catalonia, from January 2011 to December 2018. The most frequent indications were bullous keratopathy (BK; 20.5%), Fuchs endothelial dystrophy (FED; 17.9%), re-graft (13.7%), and keratoconus (11.3%). Penetrating keratoplasty (PKP) accounted for 63.4% of all performed keratoplasties. Since the introduction of eye bank precut tissue for Descemet stripping automated endothelial keratoplasty (DSAEK) in 2013 and for Descemet membrane endothelial keratoplasty (DMEK) in 2017 the number of endothelial keratoplasties has drastically increased. An increasing trend of posterior lamellar techniques over the total of keratoplasties was found (p<0.001). Endothelial keratoplasties for different endothelial diseases indications (BK, FED, and re-graft), also showed and increasing trend (p<0.001). DMEK is the technique with the highest increase (statistically significantly different from linearity) over other endothelial keratoplasties in FED (p<0.001) but not in BK (p = 0.67) or re-grafts (p = 0.067). Conclusion: Endothelial diseases represented the top indication for keratoplasty over the 8-year period. PKP is still the most used technique in Catalonia, but endothelial keratoplasties and especially DMEK showed a significant increasing trend over the last years. This is congruent withthe main rationale nowadays for keratoplasties: to customize and transplant as less tissue as possible. Therefore, the availability of precut tissue could have definitely enforced such approach

The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS

BACKGROUND: Multiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations. FINDINGS: The MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway. DISCUSSION: The analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients

Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H

Age-related macular degeneration (AMD) heads the list of legal blindness among the elderly population in developed countries. Due to the complex nature of the retina and the variety of risk factors and mechanisms involved, the molecular pathways underlying AMD are not yet fully defined. Persistent low-grade inflammation and oxidative stress eventually lead to retinal pigment epithelium dysfunction and outer blood-retinal barrier (oBRB) breakdown. The identification of AMD susceptibility genes encoding complement factors, and the presence of inflammatory mediators in drusen, the hallmark deposits of AMD, supports the notion that immune-mediated processes are major drivers of AMD pathobiology. Complement factor H (FH), the main regulator of the alternative pathway of the complement system, may have a key contribution in the pathogenesis of AMD as it is able to regulate both inflammatory and oxidative stress responses in the oBRB. Indeed, genetic variants in the CFH gene account for the strongest genetic risk factors for AMD. In this review, we focus on the roles of inflammation and oxidative stress and their connection with FH and related proteins as regulators of both phenomena in the context of AMD

Anatomic Response to Intravitreal Dexamethasone Implant and Baseline Aqueous Humor Cytokine Levels in Diabetic Macular Edema

Dexamethasone; Cytokine; Macular EdemaDexametasona; Citocina; Edema macularDexametasona; Citosina; Edema macularPURPOSE: To determine whether baseline cytokine aqueous humor (AH) levels are associated with diabetic macular edema (DME) anatomic response to dexamethasone intravitreal implant (DEX) injection. METHODS: This was a prospective cohort study of DME cases receiving DEX treatment. Seventy patients were recruited with center-involving DME with spectral-domain (SD) optical coherence tomography (OCT) detection of central macular thickness (CMT) ≥300 μm on macular cube 518 × 128-μm scan protocol (Cirrus SD-OCT). DEX injection and anterior chamber tap to obtain an AH sample were performed at the same time. Multiplex immunoassay was carried out for interleukin (IL)-1β, IL-3, IL-6, IL-8, IL-10; monocyte chemoattractant protein (MCP)-1; interferon gamma-induced protein (IP)-10; tumor necrosis factor (TNF)-α; and vascular endothelial growth factor (VEGF). A follow-up visit and OCT exam were undertaken 6 to 8 weeks afterward. The association between AH cytokine baseline levels and change in CMT and macular volume (MV) was defined as main outcome measure. RESULTS: Multivariate linear regression analysis showed a higher decrease in MV to be associated (Rs of 0.512) with four baseline items: higher MCP-1 (β = -0.4; P = 0.028), higher CMT (β = -0.003; P = 0.024), decreased visual acuity (β = -0.7; P = 0.040), and a diffuse retinal thickening (DRT) OCT pattern (β = -1.3; P < 0.001). Logistic regression found DRT also to be associated with higher odds of a good MV response (odds ratio, 31.96; 95% confidence interval [CI] 7.11-143.72; P < 0.001). CONCLUSIONS: Even though visual acuity response and anatomic effect are not always correlated in DME, we found that baseline elevated MCP-1 AH levels and DRT pattern were biomarkers that predicted a future favorable anatomic response to DEX

C-reactive protein isoforms as prognostic markers of COVID-19 severity

C-reactive protein (CRP), an active regulator of the innate immune system, has been related to COVID-19 severity. CRP is a dynamic protein undergoing conformational changes upon activation in inflammatory microenvironments between pentameric and monomeric isoforms. Although pentameric CRP is the circulating isoform routinely tested for clinical purposes, monomeric CRP shows more proinflammatory properties. Therefore, we aimed to determine the potential of monomeric CRP in serum as a biomarker of disease severity in COVID-19 patients (admission to intensive care unit [ICU] and/or in-hospital mortality). We retrospectively determined clinical and biological features as well as pentameric and monomeric CRP levels in a cohort of 97 COVID-19 patients within 72h of hospital admission. Patients with severe disease had higher levels of both pentameric and monomeric CRP. However, multivariate analysis showed increased mCRP but not pCRP to be independently associated to disease severity. Notably, mCRP levels higher than 4000 ng/mL (OR: 4.551, 95% CI: 1.329-15.58), together with number of co-morbidities, low lymphocyte count, and procalcitonin levels were independent predictors of disease severity in the multivariate model. Our results show the potential of mCRP levels as a marker of clinical severity in COVID-19 disease

Progression of Retinal Ganglion Cell and Nerve Fiber Layer Loss in Spinocerebellar Ataxia 3 Patients

Spectral domain optical coherence tomography (SD-OCT) allows noninvasive measurements of retinal neuron layers. Here, we evaluate the relationship between clinical features and anatomical SD-OCT measurements in patients with spinocerebellar ataxia type 3 (SCA3) and how they change with time. A retrospective review was conducted on SCA3 patients. Clinical variables such as disease duration, number of CAG repeats, and the Scale for the Assessment and Rating of Ataxia (SARA) score were correlated with SD-OCT measurements, including retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, macular volume (MV), and central macular thickness (CMT). Seventeen SCA3 patients with an average follow-up of 44.9 months were recruited. Clinical features with significant baseline correlations with SD-OCT measurements included disease duration (CMT r = - 0.590; GCC r = - 0.585), SARA score (CMT r = - 0.560; RNFL r = - 0.390), and number of CAG repeats (MV r = - 0.552; RNFL r = - 0.503; GCC r = - 0.493). The annual rate of change of the SARA score during follow-up was associated with that of both the MV (r = - 0.494; p = 0.005) and GCC thickness (r = - 0.454; p = 0.012). High disability (stages 2 and 3) was independently inversely associated with the annual change in MV (ß coefficient - 17.09; p = 0.025). This study provides evidence of an association between clinical features and objective anatomical measurements obtained by SD-OCT in SCA3 patients. MV and GCC thickness could serve as potential biomarkers of disease severity, as their rates of decrease seem to be related to a worsening in the SARA score. These findings highlight the potential of SD-OCT as a noninvasive tool for assessing disease severity and progression in SCA3 patients.<br /

Activation of C-reactive protein proinflammatory phenotype in the blood retinal barrier in vitro: implications for age-related macular degeneration

The retinal pigment epithelium (RPE) is considered one of the main targets of age-related macular degeneration (AMD), the leading cause of irreversible vision loss among the ageing population worldwide. Persistent low grade inflammation and oxidative stress eventually lead to RPE dysfunction and disruption of the outer blood-retinal barrier (oBRB). Increased levels of circulating pentameric C-reactive protein (pCRP) are associated with higher risk of AMD. The monomeric form (mCRP) has been detected in drusen, the hallmark deposits associated with AMD, and we have found that mCRP induces oBRB disruption. However, it is unknown how mCRP is generated in the subretinal space. Using a Transwell model we found that both pCRP and mCRP can cross choroidal endothelial cells and reach the RPE in vitro and that mCRP, but not pCRP, is able to cross the RPE monolayer in ARPE-19 cells. Alternatively, mCRP can originate from the dissociation of pCRP in the surface of lipopolysaccharide-damaged RPE in both ARPE-19 and primary porcine RPE lines. In addition, we found that the proinflammatory phenotype of mCRP in the RPE depends on its topological localization. Together, our findings further support mCRP contribution to AMD progression enhancing oBRB disruption

C-reactive protein conformations and their association with the IL-1β/IL-6 pathway in ocular inflammatory conditions

IntroductionC-reactive protein (CRP) plays a critical role in the innate immune system and serves as a biomarker for various inflammatory conditions. CRP is a dynamic protein undergoing conformational changes between pentameric (pCRP) and monomeric (mCRP) conformations. pCRP is the well-established systemic marker of inflammation, while mCRP is associated with localized tissue inflammation.MethodsThis study aimed to evaluate systemic levels of pCRP, mCRP, interleukin-6 (IL-6), and interleukin-1β (IL-1β) in patients with a variety of intraocular inflammatory conditions, including diabetic macular edema (DME) and non-infectious uveitis such as Behçet’s disease (BD), Birdshot retinochoroidopathy (BSRC), HLA-B27-associated uveitis, and undifferentiated uveitis (UU).ResultsA total of 77 subjects were included. mCRP levels were significantly elevated in BD, DME, and UU compared to controls (p = 0.014, p = 0.036, and p = 0.031, respectively). The mCRP/pCRP ratio was also significantly higher in DME and UU (p = 0.035 and p = 0.011, respectively). In addition, a strong positive correlation was observed between IL-6 and IL-1β (ρ = 0.638, p &lt;0.0001). No significant differences in serum levels of pCRP, IL-6, or IL-1β were observed among the groups.ConclusionsThese findings suggest that mCRP, rather than pCRP, may be a more specific systemic biomarker for certain intraocular inflammatory conditions. The involvement of the CRP axis and the strong correlation between IL-6 and IL-1β underscore the interaction of these key inflammatory mediators, providing further insight into the targeting of CRP axis for therapeutic purposes