Vitreorretinopatía proliferativa y retinopatía diabética proliferativa: caracterización celular y glucoproteínas de adhesión de la matriz extracelular

[spa] El presente trabajo está estructurado en dos bloques bajo un tema común: la enfermedad proliferativa intraocular. En el primer bloque se presenta, a modo de revisión bibliográfica general, la vitreorretinopatía proliferativa y la retinopatía diabética proliferativa. En el segundo bloque se presenta nuestra aportación experimental al estudio de las membranas fibrocelulares y fibrogliovasculares de ambas patologías, así estructurado: (1) la morfología y la ultraestructura de los componentes celulares, capilares y de la matriz extracelular, así como un estudio estereológico de la estimación matriz-volumen celular de estos tejidos; (2) la expresión de las proteinas de los filamentos intermedios de los diferentes tipos celulares involucrados en la formación de estas membranas; (3) la expresión de la fibronectina, la laminina, la vitronectina, y sus receptores (Alfa V-Beta 3 y Beta 1) en los capilares de neoformación y láminas basales que constituyen las membranas fibrogliovasculares de retinopatía diabética proliferativa. Asímismo, se evalúan las concentraciones de proteínas totales, fibronectina y vitronectina en muestras vítreas normales y patológicas; (4) el análisis de los cambios de expresión de estas glucoproteinas y sus receptores en las membranas epirretinianas de la vitreorretinopatía proliferativa, y las alteraciones de concentración intravitrea de fibronectina y vitronectina en los diferentes estadios clínicos de evolución de esta patología. La metodologia experimental está constituida básicamente por técnicas convencionales de microscopia óptica y electrónica, técnicas inmunocitoquímicas para microscopio óptico y electrónico de transmisión, electroforesis de proteínas, técnicas de inmunotransferencia, y cuantificaciones densitométricas mediante análisis de imágenes

Vitreorretinopatía proliferativa y retinopatía diabética proliferativa: caracterización celular y glucoproteínas de adhesión de la matriz extracelular

[spa] El presente trabajo está estructurado en dos bloques bajo un tema común: la enfermedad proliferativa intraocular. En el primer bloque se presenta, a modo de revisión bibliográfica general, la vitreorretinopatía proliferativa y la retinopatía diabética proliferativa. En el segundo bloque se presenta nuestra aportación experimental al estudio de las membranas fibrocelulares y fibrogliovasculares de ambas patologías, así estructurado: (1) la morfología y la ultraestructura de los componentes celulares, capilares y de la matriz extracelular, así como un estudio estereológico de la estimación matriz-volumen celular de estos tejidos; (2) la expresión de las proteinas de los filamentos intermedios de los diferentes tipos celulares involucrados en la formación de estas membranas; (3) la expresión de la fibronectina, la laminina, la vitronectina, y sus receptores (Alfa V-Beta 3 y Beta 1) en los capilares de neoformación y láminas basales que constituyen las membranas fibrogliovasculares de retinopatía diabética proliferativa. Asímismo, se evalúan las concentraciones de proteínas totales, fibronectina y vitronectina en muestras vítreas normales y patológicas; (4) el análisis de los cambios de expresión de estas glucoproteinas y sus receptores en las membranas epirretinianas de la vitreorretinopatía proliferativa, y las alteraciones de concentración intravitrea de fibronectina y vitronectina en los diferentes estadios clínicos de evolución de esta patología. La metodologia experimental está constituida básicamente por técnicas convencionales de microscopia óptica y electrónica, técnicas inmunocitoquímicas para microscopio óptico y electrónico de transmisión, electroforesis de proteínas, técnicas de inmunotransferencia, y cuantificaciones densitométricas mediante análisis de imágenes

Topical azithromycin or ofloxacin for endophthalmitis prophylaxis after intravitreal injection.

Background: The number of patients who have undergone intravitreal injections has increased enormously in recent years, but a consensus is still lacking on prophylaxis for endophthalmitis. The aim of this prospective, observational study was to evaluate the prophylactic effect of azithromycin eye drops versus ofloxacin eye drops. Methods: The study was conducted in five hospitals in Spain and included all patients under going intravitreal injections of triamcinolone, bevacizumab, ranibizumab, or pegaptanib over one year. Patients received azithromycin 15 mg/g eye drops (twice daily on the day prior to injection and for another 2 days) or ofloxacin 3 mg/g eye drops (every 6 hours on the day prior to injection and for another 7 days). Results: In the azithromycin group, there were 4045 injections in 972 eyes of 701 patients. In the ofloxacin group, there were 4151 injections in 944 eyes of 682 patients. There were two cases of endophthalmitis (0.049%) in the azithromycin group and five (0.12%) in the ofloxacin group. The odds ratio of presenting with endophthalmitis in the ofloxacin group compared with the azithromycin group was 2.37 (95% confidence interval [CI] 1.32-3.72, P ,0.001). There were two cases of noninfectious uveitis after triamcinolone injection in the azithromycin group (0.049%) and two (0.048%) in the ofloxacin group; no significant differences were observed (odds ratio 0.902, 95% CI 0.622-1.407, P= 0.407). Conjunctival hyperemia was observed in 12 cases in the azithromycin group and none in the ofloxacin group. Conclusion: The risk of endophthalmitis was significantly greater with ofloxacin than with azithromycin. These findings provide a valuable addition to the ever-increasing pool of infor - mation on endophthalmitis prophylaxis after intravitreal injection, although further large-scale studies are required to provide definitive conclusions

Epimacular brachytherapy for wet AMD: current perspectives

Age-related macular degeneration (AMD) is considered the most common cause of blindness in the over-60 age group in developed countries. There are basically two forms of presentation: geographic (dry or atrophic) and wet (neovascular or exudative). Geographic atrophy accounts for approximately 85%-90% of ophthalmic frames and leads to a progressive degeneration of the retinal pigment epithelium and the photoreceptors. Wet AMD causes the highest percentage of central vision loss secondary to disease. This neovascular form involves an angiogenic process in which newly formed choroidal vessels invade the macular area. Today, intravitreal anti-angiogenic drugs attempt to block the angiogenic events and represent a major advance in the treatment of wet AMD. Currently, combination therapy for wet AMD includes different forms of radiation delivery. Epimacular brachytherapy (EMBT) seems to be a useful approach to be associated with current anti-vascular endothelial growth factor agents, presenting an acceptable efficacy and safety profile. However, at the present stage of research, the results of the clinical trials carried out to date are insufficient to justify extending routine use of EMBT for the treatment of wet AMD

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

Simultaneous retinal pigment epithelium tear and lamellar macular hole evolving to a full-thickness macular hole after intravitreal therapy

Retinal pigment epithelium (RPE) tear is an uncommoncomplication of neovascular age-related macular degenera-tion (nAMD) with an increasing risk in cases with pigmentepithelium detachment (PED) and may appear sponta-neously or after intravitreal therapy (IVT). Other uncommoncomplications of IVT related to nAMD are lamellar macularhole (LMH) and full-thickness macular hole (FTMH). Here, wepresent a patient with nAMD that developed a RPE tear asso-ciated with LMH that evolved into a FTMH two months laterafter IVT with ranibizumab (Lucentis®). Long-term follow-upwas registered

Intraocular pressure after myopic laser refractive surgery measured with a new Goldmann convex prism: correlations with GAT and ORA

Background: The purpose of this study is to describe measurements using a newly developed modified Goldmann convex tonometer (CT) 1 year after myopic laser refractive surgery. Intraocular pressure (IOP) measurements were compared with IOP values obtained by Goldmann applanation tonometer (GAT), and Ocular Response Analyzer (ORA). Methods: Prospective double-masked study performed on thirty eyes of thirty patients that underwent laser in situ keratomileusis (LASIK; n = 19) or photorefractive keratectomy (PRK; n = 11). IOP was measured before and 3 and 12 months after surgery. Intraclass correlation coefficient (ICC) and Bland-Altman plot were calculated to assess the agreement between GAT, CT, IOPg (Goldmann-correlated IOP) and IOPcc (corneal-compensated IOP) from ORA. Results: Twelve months after LASIK, IOP measured with CT showed the best correlation with IOP measured with GAT before surgery (GATpre) (ICC = 0.886, 95% CI: 0.703-0.956) (15.60 ± 3.27 vs 15.80 ± 3.22; p < 0.000). However, a moderate correlation was found for IOP measured with IOPcc and CT 12 months after LASIK (ICC = 0.568, 95% CI: − 0.185 - 0.843) (15.80 ± 3.22 vs 12.87 ± 2.77; p < 0.004). Twelve months after PRK, CT showed a weak correlation (ICC = − 0.266, 95% CI: − 3.896 - 0.663), compared to GATpre (17.30 ± 3.47 vs 16.01 ± 1.45; p < 0.642), as well as poor correlation (ICC = 0.256, 95% CI: − 0.332 - 0.719) with IOPcc (17.30 ± 3.47 vs 13.38 ± 1.65; p < 0.182). Conclusions: Twelve months after LASIK, IOP measured with CT strongly correlated with GAT before surgery and could therefore provide an alternative method for measuring IOP after this surgery. More studies regarding this new convex prism are needed to assess its accuracy. Keywords: Tonometry, Corneal biomechanics, Intraocular pressure, Glaucoma, Myopia, LASIK, PR

Potential Role of Induced Pluripotent Stem Cells (IPSCs) for Cell-Based Therapy of the Ocular Surface

The integrity and normal function of the corneal epithelium are crucial for maintaining the cornea's transparency and vision. The existence of a cell population with progenitor characteristics in the limbus maintains a dynamic of constant epithelial repair and renewal. Currently, cell-based therapies for bio replacement cultured limbal epithelial transplantation (CLET) and cultured oral mucosal epithelial transplantation (COMET) present very encouraging clinical results for treating limbal stem cell deficiency (LSCD) and restoring vision. Another emerging therapeutic approach consists of obtaining and implementing human progenitor cells of different origins in association with tissue engineering methods. The development of cell-based therapies using stem cells, such as human adult mesenchymal or induced pluripotent stem cells (IPSCs), represent a significant breakthrough in the treatment of certain eye diseases, offering a more rational, less invasive, and better physiological treatment option in regenerative medicine for the ocular surface. This review will focus on the main concepts of cell-based therapies for the ocular surface and the future use of IPSCs to treat LSCD

New applanation tonometer for myopic patients after laser refractive surgery

This study assesses the agreement between intraocular pressure (IOP) measurements taken with the Goldmann applanation tonometer (GAT) and a new experimental applanation tonometer with a convexly shaped apex (CT) after laser myopic refractive surgery. Two different CT radii (CT1 and CT2) were designed with a finite element analyser, and a prospective double masked study on 102 eyes from 102 patients was carried out. A Bland-Altman plot and intra-class correlation coefficient (ICC) were calculated to assess the agreement between GAT measurements and the measurements of both CT1 and CT2 before and after myopic laser assisted in situ keratomileusis (LASIK; n = 73) and photorefractive keratectomy (PRK; n = 29). We evaluated a subset of two subgroups (n = 36 each) for intra and inter-observer (IA/IE) error. From the whole cohort, the best IOP agreement was observed between GATpre and CT1post surgery: 16.09 ± 2.92 vs 16.42 ± 2.87 (p 0.8 (95% CI) in all cases. CT1 proved more accurate in the LASIK subgroup. In conclusion, our new version of GAT could be used with post-surgery LASIK patients as a more accurate measurement device compared to the current reference tonometer

Extrinsic modulation of integrin α6 and progenitor cell behavior in mesenchymal stem cells

Mesenchymal stem cells (MSC) are heterogeneous cells of complex nature that show different potentials while different culture conditions can modify their functionalities through interactions with the microenviroment. Here, we found that bone marrow (BM) MSC from different donor sources and passages that expressed higher levels of α6 integrin subunit (ITGA6), showed higher clonogenicity, migration and differentiation potential. ITGA6 showed important roles improving these potentials and regulating proliferation through protein kinase B (AKT) pathway and cell cycle inhibitor proteins p53 and p21. Moreover, ITGA6 downregulation impaired migration. Cell confluence regulated ITGA6, increasing its expression in low density cultures and decreasing in high density cultures. Besides, ITGA6- cells expressed ITGA6 when seeded at low densities. We found higher ITGA6 expression on fibronectin substrates at lower confluency. Fibronectin increased proliferation, clonogenicity, activation of AKT, decreased cell cycle inhibitor proteins and augmented growth factors expression. Spheres-derived MSC showed higher ITGA6 expression and enhanced potentials for migration, clonogenicity and proliferation. In conclusion, though there is an intrinsic regulation of ITGA6 expression, associated to the progenitor potential of BM-MSC, this expression is regulated by culture conditions and is translated in changes in cell behavior and proliferation. This knowledge could be used to enhance the potential of BM-MSC for clinical application