Tratamiento de la rosácea ocular: revisión práctica desde un enfoque interdisciplinario / Treatment of ocular rosacea: A practical review from an interdisciplinary approach

La rosácea es una enfermedad crónica e inflamatoria que afecta principalmente la piel, aunque más de la mitad de los casos también presentan síntomas oculares. Estos pueden ir desde blefaritis hasta conjuntivitis y queratitis. Representa un motivo de consulta frecuente con un impacto psicosocial y en la calidad de vida; su manejo compete tanto a oftalmólogos, dermatólogos y médicos de primer contacto. Para esta investigación, se llevó a cabo una búsqueda en varias bases de datos, incluyendo Medline, Embase, Cochrane y Google Scholar. Se utilizó el término MeSH «rosácea» junto con otras palabras clave relevantes, como «rosácea ocular», «manejo», «tratamiento» y «guías». Se revisaron los artículos disponibles. Las principales guías internacionales y locales recomiendan iniciar el manejo con cambios en el estilo de vida, con especial énfasis en la higiene ocular y evitación de desencadenantes. Como siguiente paso, se recomienda el tratamiento tópico u oral, siendo la ciclosporina tópica, la azitromicina tópica, el tacrolimús tópico y la doxiciclina oral los tratamientos más respaldados por la evidencia. Se recomienda combinar tratamientos. Las guías de manejo actuales se concentran principalmente en las manifestaciones cutáneas y generan pocas directrices sobre el tratamiento oftalmológico. La mayoría de las recomendaciones son emitidas por expertos. En este trabajo, se comparan las guías de tratamiento locales e internacionales de la rosácea, así como otra literatura médica disponible, y se sugiere un esquema de tratamiento práctico e interdisciplinario para la afección ocular basado en la bibliografía revisada (AU)

Rosacea is a chronic and inflammatory disease that primarily affects the skin, although more than half of cases also present with ocular symptoms ranging from blepharitis to conjunctivitis and keratitis. It represents a frequent reason for consultation with a psychosocial impact, affecting quality of life, and requires management involving ophthalmologists, dermatologists, and primary care physicians. For this paper, a search was conducted in several databases, including Medline, Embase, Cochrane, and Google Scholar, using the MeSH term “rosacea” in conjunction with other relevant keywords such as “ocular rosacea”, “management”, “treatment”, and “guidelines”. Available articles were reviewed. International and local guidelines recommend initiating the management of rosacea with lifestyle changes, including ocular hygiene and avoidance of triggers. Topical or oral treatment is recommended as the next step, with topical cyclosporine, topical azithromycin, topical tacrolimus, and oral doxycycline being the treatments most supported by evidence. Combination treatments are also recommended. Current management guidelines mainly focus on cutaneous manifestations, generating few guidelines on ophthalmologic treatment, and most recommendations are issued by experts. This work compares local and international treatment guidelines for rosacea, as well as other available medical literature, and suggests a practical and interdisciplinary treatment scheme for ocular involvement based on the reviewed bibliography (AU)

Treatment of ocular rosacea: A practical review from an interdisciplinary approach.

Rosacea is a chronic and inflammatory disease that primarily affects the skin, although more than half of cases also present with ocular symptoms ranging from blepharitis to conjunctivitis and keratitis. It represents a frequent reason for consultation with a psychosocial impact, affecting quality of life, and requires management involving ophthalmologists, dermatologists, and primary care physicians. For this paper, a search was conducted in several databases, including Medline, Embase, Cochrane, and Google Scholar, using the MeSH term "rosacea" in conjunction with other relevant keywords such as "ocular rosacea", "management", "treatment", and "guidelines". Available articles were reviewed. International and local guidelines recommend initiating the management of rosacea with lifestyle changes, including ocular hygiene and avoidance of triggers. Topical or oral treatment is recommended as the next step, with topical cyclosporine, topical azithromycin, topical tacrolimus, and oral doxycycline being the treatments most supported by evidence. Combination treatments are also recommended. Current management guidelines mainly focus on cutaneous manifestations, generating few guidelines on ophthalmologic treatment, and most recommendations are issued by experts. This work compares local and international treatment guidelines for rosacea, as well as other available medical literature, and suggests a practical and interdisciplinary treatment scheme for ocular involvement based on the reviewed bibliography.

Alginate electrodeposition onto three-dimensional porous Co-Ni films as drug delivery platforms.

Three-dimensional porous Co-Ni films/alginate hybrid materials have been successfully prepared by electrodeposition to be used as a steerable magnetic device for drug delivery. Firstly, 3D porous Co-Ni films were prepared as substrates for the subsequent electrodeposition of the alginate biopolymer. Cyclic voltammetry, galvanostatic and potentiostatic studies were performed to establish the best conditions to obtain porous Co-Ni films. The electrochemical experiments were carried out in an electrolyte containing the metal salts and ammonium chloride at low pHs. In a second stage, the electrochemical deposition of alginate as a biocompatible polymer drug delivery carrier was performed. The characteristics of the alginate matrix were investigated in terms of electrochemical properties, morphology and drug release. The hybrid material obtained showed soft-magnetic behavior and drug release indicating its suitability to be used as a steerable magnetic drug delivery device.

First Report of Wood Canker Caused by Neoscytalidium dimidiatum on Grapevine in California.

In May 2012 in the Coachella valley, Riverside County, California, the decline of vines in table grape (Vitis vinifera) vineyards was observed. Foliar symptoms consisted of shoot blight with wilting and necrosis of leaves and drying and shriveling of berries. In some cases, the entire vine collapsed in the middle of the growing season (apoplexia). Wood cankers in the spurs, cordons, and trunks of affected vines were also present. The nine isolates recovered from the cankers were identified as Neoscytalidium dimidiatum (Penz.) Crous & Slippers based on morphological characteristics and DNA sequence comparisons. Two isolates were grown on potato dextrose agar (PDA) medium and a total of 50 conidia were measured per isolate. Conidia were ellipsoid to ovoid, with a truncate base and an acutely rounded apex, initially aseptate, becoming brown and two-celled at maturity, 7.2 ± 1.2 µm × 3.8 ± 0.4 µm. The rDNA internal transcribed spacer (ITS), and ß-tubulin (BT) loci were amplified using primer pairs and methods previously described (4). A total of five isolates were sequenced. The DNA sequences of one N. dimidiatum grapevine isolate (UCR-Neo1) were deposited in the GenBank database (ITS, KC937066; BT, KC937067). Pathogenicity tests were performed by inoculating 12 grape cuttings cv. Thompson Seedless with isolate UCR-Neo1 and 12 control cuttings with sterile medium using a technique previously described (1). The experiment was repeated twice. After 20 weeks of incubation period in the greenhouse, the lesions length produced by N. dimidiatum averaged 13.5 mm and was significantly longer (P < 0.05) from the control (average 3 mm). N. dimidiatum was reisolated from all the inoculated plants and identified by colony morphology. The incidence of N. dimidiatum in table grape vineyards of the Coachella valley has been estimated at 15%, with nine vines infected out of 60 vines total. This pathogen has been identified in California in walnut nursery causing the death of trees due to the development of canker at the graft union (2). N. dimidiatum has also been identified as the causal agent of shoot blight, canker, and gummosis on citrus in Italy (3). The crop is also being grown in the Coachella valley and these findings warrant further investigation in order to determine the host range, distribution, and incidence of this pathogen in the area. References: (1) K. Baumgartner et al. Plant Dis. 97:912, 2013. (2) S. F. Chen et al. Plant Dis. 97:993, 2013. (3) G. Polizzi et al. Plant Dis 93:1215, 2009. (4) J. R. Urbez-Torres et al. Plant Dis. 92:519, 2008.

Botryosphaeriaceae Species Spore-Trapping Studies in California Vineyards.

The seasonal abundance of Botryosphaeriaceae spp. spores was studied in California vineyards by using glass microscope slides covered with petroleum jelly placed on grapevine cordons and Burkard volumetric spore traps at seven and two different locations, respectively. Correlation analysis was used to determine which meteorological variables (precipitation, relative humidity, temperature, and wind speed) influenced Botryosphaeriaceae spp. spore release. Among all variables, regression analysis resulted in a strong relationship between spore release and precipitation. Additionally, a positive relationship between irrigation and spore release was also observed in the Riverside County vineyard. During the study period, spore discharge of Botryosphaeriaceae spp. occurred from the first fall rain through the last spring rains, coinciding with September to April. However, based on the results obtained from the spore traps, most spores (over 60%) were trapped following rain events during the winter months of December, January, and February, which coincides with the grapevine pruning season. Botryosphaeriaceae spp. spore release was much lower in fall and early spring (22%) and very few or no spores were trapped in late spring and summer (3%). This work suggests that a delay of pruning time in California may be warranted to reduce grapevine infection because the current timing coincides with the greatest period of spore discharge.

Detection and differentiation of Xylella fastidiosa strains acquired and retained by glassy-winged sharpshooters (Hemiptera: Cicadellidae) using a mixture of strain-specific primer sets.

Xylella fastidiosa Wells is a bacterial pathogen that causes a variety of plant diseases, including Pierce's disease (PD) of grapevine, almond leaf scorch, alfalfa dwarf, citrus variegated chlorosis, and oleander leaf scorch (OLS). Numerous strains of this pathogen have been genetically characterized, and several different strains occur in the United States. The dominant vector in southern California is the glassy-winged sharpshooter, Homalodisca coagulata (Say) (Hemiptera: Cicadellidae). The high mobility of this insect, and its use of large numbers of host plant species, provides this vector with ample exposure to multiple strains of X. fastidiosa during its lifetime. To learn more about the ability of this vector to acquire, retain, and transmit multiple strains of the pathogen, we developed a polymerase chain reaction (PCR)-based method to detect and differentiate strains of X. fastidiosa present in individual glassy-winged sharpshooter adults. Insects were sequentially exposed to plants infected with a PD strain in grapevine and an OLS strain in oleander. After sequential exposure, a few insects tested positive for both strains (7%); however, in most cases individuals tested positive for only one strain (29% PD, 41% OLS). In transmission studies, individual adults transmitted either the PD or OLS strain of the pathogen at a rate (39%) similar to that previously reported after exposure to a single strain, but no single individual transmitted both strains of the pathogen. PD and OLS strains of X. fastidiosa remained detectable in glassy-winged sharpshooter, even when insects were fed on a plant species that was not a host of the strain for 1 wk.

Plant Hosts of Xylella fastidiosa In and Near Southern California Vineyards.

Xylella fastidiosa is a xylem-limited bacterium that causes Pierce's disease (PD) of grapevines. A variety of plant species found near a severe outbreak of PD in vineyards in the Temecula Valley of California were tested using enzyme-linked immunosorbent assay, culture on media, and polymerase chain reaction to identify potential inoculum sources in the area. Species that consistently tested positive for X. fastidiosa were the known hosts, grape, almond, and oleander, and two new hosts, Spanish broom (Spartium junceum) and wild mustard (Brassica spp). Sequence analysis of the 16S-23S rRNA spacer region found that strains isolated from grapevine, Spanish broom, wild mustard, and almond clustered with previously sequenced PD strains. Thus, these species could serve as sources of inoculum for infection of grapevines and should be removed or monitored for signs of infection. Sequences from oleander isolates from Temecula formed another cluster with a previously published oleander strain sequence. Oleander strains do not infect grapevines and thus do not appear to cause a direct threat to grapevines. Two additional isolates from almond were determined to be genetically different from PD strains, and the ability of these strains to infect grapevine is not known. Greenhouse transmission studies indicate that the glassy-winged sharpshooter was able to transmit a PD strain of X. fastidiosa to Spanish broom, black mustard, and other hosts.

Increased intracellular calcium is required for spreading of rat islet beta-cells on extracellular matrix.

Rat islet beta-cells spread in response to glucose when attached on the matrix produced by a rat bladder carcinoma cell line (804G). Furthermore, in a mixed population of cells, it has been observed previously that spread cells secrete more insulin acutely in response to glucose, compared with cells that remain rounded. These results suggest bi-directional signaling between the islet beta-cell and the extracellular matrix. In the present study, the role of increased intracellular free Ca2+ concentration [Ca2+]i as an intracellular step linking glucose stimulation and beta-cell spreading (inside-out signaling) was investigated. Purified rat beta-cells were attached to this matrix and incubated under various conditions known to affect [Ca2+]i. The effect of glucose on beta-cell spreading was mimicked by 25 mmol/l KCl (which induces calcium influx) and inhibited by diazoxide (which impairs depolarization and calcium entry) and by the L-type Ca2+ channel blocker SR-7037. When a 24-h incubation at 16.7 glucose was followed by 24 h at 2.8 mmol/l, beta-cells that had first spread regained a round phenotype. In the presence of thapsigargin, spreading progressed throughout the experiment, suggesting that capture of calcium by the endoplasmic reticulum is involved in the reversibility of spreading previously induced by glucose. Spreading was still observed in degranulated beta-cells and in botulinum neurotoxin E-expressing beta-cells when exocytosis was prevented. In summary, the results indicate that increased [Ca2+]i is required for the glucose-induced spreading of beta-cells on 804G matrix and that it is not a consequence of exocytotic processes that follow elevation of [Ca2+]i.

Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells.

The tSNARE SNAP-25 is expressed in pancreatic (beta)-cells and is involved in the regulated release of insulin. It has been shown previously that SNAP-25 associates with the plasma membrane consequent to palmitoylation of one or more cysteines in the central region of the molecule. The importance of palmitolyation in the biological function of SNAP-25 in exocytosis was not addressed. Furthermore, studies on both SNAP-25 and its non-palmitoylated homologues SNAP-29 and sec9, have suggested an alternative or complementary mechanism for membrane association involving interaction with syntaxin. To address these issues, we have now studied the behavior and biological activity of cysteine mutant SNAP-25 in insulin-secreting (HIT) cells. While 91% of native SNAP-25 was associated with the membrane, this value decreased to 56% for the single cysteine mutant C85/A and to 10% for the double (C85,88/A) and quadruple (C85,88,90,92/A) mutants. The mutant SNAP-25 forms were all found to bind syntaxin 1A with equal efficacy. Over-expression of syntaxin 1A in HIT cells allowed for partial relocalization of both the double and quadruple SNAP-25 cys mutants to the membrane. By introducing a further mutation to the SNAP-25 molecules to render them resistant to botulinum neurotoxin E, it was possible to study their ability to reconstitute regulated insulin secretion in toxin-treated HIT cells. Native SNAP-25 was able to fully reconstitute secretory activity in such cells. Despite the fact that the single cysteine mutant was significantly displaced to the cytosol, it still displayed 82% activity in the secretion reconstitution assay, and a similar discrepancy was seen for the double mutant. Even the quadruple mutant with no remaining cysteines was able to support a minimal level of secretion. It is concluded that both palmitoylation and binding to syntaxin are implicated in membrane association of SNAP-25. This as well as the discrepancy between membrane localization and biological activity of the cysteine mutants, suggests a complex, multi-component process for association of SNAP-25 with the membrane and its recruitment to a biologically productive state.

SNAP-25a and -25b isoforms are both expressed in insulin-secreting cells and can function in insulin secretion.

The tSNARE (the target-membrane soluble NSF-attachment protein receptor, where NSF is N-ethylmaleimide-sensitive fusion protein) synaptosomal-associated protein of 25 kDa (SNAP-25) is expressed in pancreatic B-cells and its cleavage by botulinum neurotoxin E (BoNT/E) abolishes stimulated secretion of insulin. In the nervous system, two SNAP-25 isoforms (a and b) have been described that are produced by alternative splicing. Here it is shown, using reverse transcriptase PCR, that messages for both SNAP-25 isoforms are expressed in primary pancreatic B and non-B cells as well as in insulin-secreting cell lines. After transfection, both isoforms can be detected at the plasma membrane as well as in an intracellular perinuclear region in the insulin-secreting cell line, HIT. To test for the functional role of the two isoforms in insulin secretion, mutant forms of SNAP-25a and b resistant against cleavage by BoNT/E were generated. Such mutant SNAP-25, when expressed in HIT cells, is not inactivated by BoNT/E and its ability to restore insulin secretion can thus be investigated. To obtain the toxin-resistant mutant isoforms, the sequence around the BoNT/E cleavage site (R176QIDRIM182) was changed to P176QIKRIT182. This is the sequence of the equivalent region of human SNAP-23 (P187-T194), which has been shown to be resistant to BoNT/E. The mutant SNAP-25 was resistant to BoNT/E in vitro and in vivo and both mutant isoforms were able to reconstitute insulin secretion from toxin-treated HIT cells.

Ahmed valve implant for uncontrolled uveitic glaucoma.

To evaluate the efficacy of the Ahmed valve implant in patients with uncontrolled uveitic glaucoma, the medical records of all patients with uncontrolled uveitic glaucoma who underwent Ahmed valve implant surgery between October 1993 and March 1996 were reviewed. Surgery was considered a success if intraocular pressure (IOP) was less than 22 mmHg and greater than 4 mmHg (with or without antiglaucoma medications) at the last postoperative visit. It was not a success when further glaucoma surgery had been performed, or chronic hypotony, phthisis, or loss of light perception occurred. Fourteen patients (14 eyes) with a mean age of 45.7 years were included. Most of them were high-risk patients, many of whom had already had cataract surgery (71.4%) and undergone one to three previous glaucoma surgeries (57.1%). Follow-up for eyes in which IOP was controlled ranged from 11 to 40 months (mean 22.6 months). Success was achieved in eight of 14 eyes (57.14%). Intraocular pressure was reduced from a mean of 32.64 +/- 7.79 mmHg (range 23-46 mmHg) with 2.78 +/- 0.57 antiglaucoma medications (range 2-4) preoperatively to 17.57 +/- 10.93 mmHg (range 0-38 mmHg) (p < 0.0001) with 0.71 +/- 0.99 antiglaucoma medications (range 0-3) postoperatively (p < 0.0001). The most common complications were encapsulated bleb in six eyes (42.8%), transient hypotony in six eyes (42.8%), and hyphema in three (21.4%). Ahmed valve implant appeared to be a safe alternative in high-risk patients with uncontrolled uveitic glaucoma who have had multiple previous ocular surgeries.

Chorioretinitis secondary to mycobacterium tuberculosis in acquired immune deficiency syndrome.

BACKGROUND: Several opportunistic intraocular infections have been described in patients with the human immunodeficiency virus, among them infections caused by Mycobacterium tuberculosis. In most cases, the diagnosis is based on clinical findings. Recent reports have described the usefulness of polymerase chain reaction techniques in the diagnosis of bacterial infections. METHODS: The authors observed a 29-year-old woman with acquired immune deficiency syndrome in whom unilateral chorioretinitis developed. The chorioretinitis appeared after cessation of treatment for pulmonary tuberculosis. We obtained aqueous humor by paracentesis and tested it by polymerase chain reaction to detect M. tuberculosis DNA. RESULTS: The polymerase chain reaction of the aqueous humor was positive for M. tuberculosis DNA. CONCLUSION: Polymerase chain reaction was useful in identifying M. tuberculosis in aqueous from a patient with chorioretinitis, pulmonary tuberculosis, and acquired immune deficiency syndrome.

Peripheral corneal endotheliopathy and pars planitis.

A peripheral corneal endotheliopathy (PCE), named autoimmune endotheliopathy was described in association with corneal graft rejection and as an isolated corneal alteration unrelated to surgery, trauma, or infection. It has also been found in patients with pars planitis (PP), but the significance of this association is unknown. The authors retrospectively reviewed the clinical charts of 53 PP patients (106 eyes) examined at the Uveitis Clinic from 1988 to 1993. Special attention was paid to the description of corneal clinical findings. PCE was found in 18.8+ of the eyes, and of these, 70+ showed bilateral involvement. The presence of PCE was not related to PP severity, but PCE was more frequently seen in younger patients. This descriptive study shows that identification of PCE may aid in the diagnosis of childhood PP.

CD8+ T lymphocytes and cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

PURPOSE: We compared the levels of CD8+ and CD4+ cells in human immunodeficiency virus (HIV)-seropositive patients who had normal eye examinations, microvasculopathy, or ocular infections other than cytomegalovirus retinitis to those of patients with cytomegalovirus retinitis, to determine whether lymphocyte counts other than CD4+ are predictive of cytomegalovirus retinitis. METHODS: The records of HIV-positive patients who had a lymphocyte subset analysis within three months of a complete eye examination were reviewed for age, gender, mode of HIV transmission, stage of disease, ocular findings, and absolute lymphocyte counts. Data for patients without cytomegalovirus retinitis were compared with those for patients with cytomegalovirus retinitis. RESULTS: Ninety-three HIV-positive patients had a lymphocyte subset analysis within three months of a complete eye examination; 76 patients had no cytomegalovirus retinitis and 17 had cytomegalovirus retinitis. Patients without cytomegalovirus retinitis and those with cytomegalovirus retinitis had the following median cell counts: CD4+, 76.0 and 15.0 cells/microliters; CD8+, 634.5 and 280.0 cells/microliters, respectively. Patients with cytomegalovirus retinitis had significantly lower CD4+ and CD8+ cell counts than those without cytomegalovirus retinitis (P < .001). CD4+ and CD8+ cells are significantly correlated with each other, and the correlation is much higher in patients with cytomegalovirus retinitis (r = .80, P < .001) than in patients without cytomegalovirus retinitis (r = .57, P < .001). Stepwise logistic regression analysis showed that CD8+ cell counts were also predictive of cytomegalovirus retinitis. CONCLUSION: Patients with low CD4+ cell counts are known to be at high risk for cytomegalovirus retinitis. We showed that patients with low CD8+ cell counts are also at high risk for cytomegalovirus retinitis.