Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF.

Neovascular retinopathies are leading causes of irreversible blindness. Although vascular endothelial growth factor (VEGF) inhibitors have been established as the mainstay of current treatment, clinical management of these diseases is still limited. As retinal impairment involves abnormal neovascularization and neuronal degeneration, we evaluated here the involvement of galectin-1 in vascular and non-vascular alterations associated with retinopathies, using the oxygen-induced retinopathy (OIR) model. Postnatal day 17 OIR mouse retinas showed the highest neovascular profile and exhibited neuro-glial injury as well as retinal functional loss, which persisted until P26 OIR. Concomitant to VEGF up-regulation, galectin-1 was highly expressed in P17 OIR retinas and it was mainly localized in neovascular tufts. In addition, OIR induced remodelling of cell surface glycophenotype leading to exposure of galectin-1-specific glycan epitopes. Whereas VEGF returned to baseline levels at P26, increased galectin-1 expression persisted until this time period. Remarkably, although anti-VEGF treatment in P17 OIR improved retinal vascularization, neither galectin-1 expression nor non-vascular and functional alterations were attenuated. However, this functional defect was partially prevented in galectin-1-deficient (Lgals1-/-) OIR mice, suggesting the importance of targeting both VEGF and galectin-1 as non-redundant independent pathways. Supporting the clinical relevance of these findings, we found increased levels of galectin-1 in aqueous humor from patients with proliferative diabetic retinopathy and neovascular glaucoma. Thus, using an OIR model and human samples, we identified a role for galectin-1 accompanying vascular and non-vascular retinal alterations in neovascular retinopathies.

Lens opacity based modelling of the age-related straylight increase.

This work studies ethnic and geographical differences in the age-related straylight increase by means of a stochastic model and unpublished lens opacity data of 559 residents of Villa Maria (Argentina), as well as data of 912 Indonesian subjects published previously by Husain et al. For both cohorts the prevalence of each type and grade of lens opacity was determined as a function of age, from which a stochastic model was derived capable of simulating the lens opacity prevalence for both populations. These simulated lens opacity data were then converted to estimated straylight by means of an equation derived from previously recorded data of 107 eyes with varying degrees of cataract. Based on these opacity templates 2500 random sets of subject age and lens opacity data were generated by the stochastic model for each dataset, from which estimated straylight could be calculated. For the Argentinian data the estimated straylight was found to closely resemble the published models for age-related straylight increase. For younger eyes the straylight variation of the model was the same as what was previously published (in both cases ±0.200logunits), which doubled in size for older eyes. For the Indonesian data, however, this age-related straylight increase was found to be fundamentally different from the published age model. This suggests that current normative curves for age-related straylight increase may not always be appropriate for non-European populations, and that the inter-individual straylight variations in young, healthy eyes may possibly be due to variations in lens opacities.

Long-term hypotony because of accidental break of a 23 g microcannula after transconjunctival sutureless vitrectomy.

PURPOSE: To report a case of long-lasting hypotony because of accidental break, with scleral tunnel entrapment, of a 23-gauge microcannula during transconjunctival sutureless vitrectomy. METHODS: Interventional case report. An 80-year-old Spanish woman who underwent 23-gauge transconjunctival sutureless vitrectomy presented at the postoperative ocular examination with irreversible, refractory low intraocular pressure of unknown cause. Two weeks after surgery, a piece of the microcannula was found at the inferotemporal sclerotomy site during a scheduled medical appointment. Surgical intervention was indicated to explore and remove the foreign body. RESULTS: The day after foreign body extraction, the patient's pressure rose to normal levels. However, her visual acuity did not improve until 3 weeks later. CONCLUSION: Transient postoperative hypotony is unsurprising after 23-gauge vitrectomy because of leakage of small-diameter open sclerotomies. However, when long-term low intraocular pressure fails to return to normal levels because of an unidentified condition, breaking of the microcannula piece with scleral tunnel entrapment may be contemplated.

Stenotrophomonas maltophilia endophthalmitis caused by surgical equipment contamination: an emerging nosocomial infection.

PURPOSE: We report three cases of Stenotrophomonas maltophilia endophthalmitis after uneventful extracapsular cataract extraction with intraocular lens implantation-related to surgical equipment contamination. CASE REPORT: All patients developed acute, culture-positive endophthalmitis in a period ranging from 2 to 13 days. Cultures from vitreous tap, as well as those obtained from the hand-piece of the irrigation-aspiration system, revealed S. maltophilia as the causing infectious agent. All patients received intravitreal antibiotic treatment as initial therapy, nevertheless, visual disturbance continued to be present, hence pars plana vitrectomy was required. CONCLUSION: Contamination of surgical-reusable equipment should be considered in addition to the well-known risk factors associated with development of endophthalmitis by S. maltophilia.

Self-medication in ophthalmology: a questionnaire-based study in an Argentinean population.

PURPOSE: The aim of this study was to identify practices of self-medication in the treatment of ocular conditions and to identify a profile of patients who self-medicate. METHODS: We conducted a cross-sectional descriptive survey of patients, over the age of 17 years seen in our ophthalmology practice in Cordoba, Argentina. Self-medication was defined as the use of ophthalmic medicines which had not been prescribed by a health care specialist in the previous year. RESULTS: The sample included 379 subjects, 162 males (43%) and 217 females (57%); mean age 46.8 years. Prior to looking for medical attention in our institution, 97 patients (25.6%) reported self-medicating. The most frequently employed products included non-steroidal anti-inflammatory drops in combination with a vasoconstrictive agent (32%) followed by a combination of antibiotics and steroids (9%), however, 14% of patients did not remember the name or type of medication applied. A total of 31% of patients used drugs recommended by a pharmacist; 25% used drugs of their own choosing and 24% followed suggestions from a friend or family member. Only 12% of patients knew the drug's components and only 3% were aware of any possible side effects. There was no difference in behavior patterns related to educational level or age, however, there was a significant difference related to gender, with males misusing ophthalmic drops more frequently than women (P = 0.004). CONCLUSIONS: Patients commonly attempt to treat conditions that require ophthalmologic care by self-medicating with over-the-counter eye drops. Educational efforts to inform patients of the consequences of self-medication are necessary.

Delayed corneal epithelial healing after intravitreal bevacizumab: a clinical and experimental study.

PURPOSE: To report corneal epithelial defects (CEDs) and delayed epithelial healing after intravitreal bevacizumab (IVB) injection and to describe delayed corneal epithelial healing with topical administration of bevacizumab in an experimental rabbit model. METHODS: A retrospective chart review was performed on 850 eyes of 850 patients with neovascular eye disease and diabetic macular edema who had received 1.25 to 2.5 mg IVB. In the experimental arm of the study, photorefractive keratectomy was used to create a 3 mm CED in the right eyes of 18 New Zealand rabbits which were then randomized to three equal groups. All rabbits received topical antibiotics, additionally those in group A received topical bevacizumab and animals in group B were treated with topical corticosteroids. The rate of epithelial healing was assessed at different time points using slitlamp photography. RESULTS: In the clinical study, seven eyes of seven subjects developed CEDs the day after IVB injection. All of these eyes had preexisting corneal edema. The healing period ranged from 3 to 38 days (average 11 days) despite appropriate medical management. In the experimental study, topical bevacizumab and corticosteroids both significantly hindered corneal epithelial healing at 12 and 24 hours. CONCLUSION: Bevacizumab was demonstrated to cause CEDs in clinical settings. Moreover, corneal epithelial healing was delayed by topical application of bevacizumab, in the experimental model. These short-term results suggest that corneal edema may be considered as a risk factor for epithelial defects after IVB.

Perfluorocarbon liquid vitreous delamination and wide-angle viewing system in the management of complicated diabetic retinal detachment.

PURPOSE: The authors used perfluorocarbon liquid (PFCL) and a wide-angle viewing system (WAVS) to evaluate their efficacy on tractional and combined tractional/rhegmatogenous retinal detachment (RD) secondary to proliferative diabetic retinopathy (PDR). METHODS: In a prospective, noncomparative, interventional study, 76 consecutive cases of severe PDR with tractional and combined tractional/rhegmatogenous RD were submitted to vitrectomy en bloc excision technique using a WAVS and delamination with PFCL between July 1999 and December 2003. None of the patients had had previous retinal photocoagulation treatment. Preoperative characteristics, intraoperative findings, and procedures as well as postoperative results were recorded. Main outcome measures included visual acuity (VA) and rates of retinal reattachment and complications. RESULTS: After 1 to 4 years of follow-up (mean 34.3 months), the number of patients changed from 3 (3.95%) to 11 patients (14.47%) in the > or =20/40 VA range, from 12 (15.79%) to 7 (9.21%) in the 20/50 to 20/200 group, and from 61 (80.26%) to 58 (76.31%) in the < or =20/400 group, preoperatively and postoperatively, respectively. The mean final VA improved from 1.2 log-MAR before surgery to 0.89 after vitrectomy (p=0.001). This modified technique resulted in less bleeding during surgery, a better identification of intraocular structures, faster retinal reattachment, subretinal fluid reabsorption, and easier dissection of fibrovascular membranes, among other benefits. CONCLUSIONS: PFCL and WAVS appear to reduce intraoperative complication rates in the management of complicated cases of tractional and combined tractional/rhegmatogenous RD secondary to PDR. Retinal reattachment and functional vision rates improved after this technique.

Effect of retinal laser photocoagulation on the activity of metalloproteinases and the alpha(2)-macroglobulin proteolytic state in the vitreous of eyes with proliferative diabetic retinopathy.

Panretinal photocoagulation (PRP) reduces the incidence of severe visual loss in proliferative diabetic retinopathy (PDR). The aim of the study was to determine the effect of PRP on the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, and also on the alpha(2)-Macroglobulin (alpha(2)M) proteolytic state in the vitreous of eyes with PDR. Vitreous samples were obtained from patients undergoing vitrectomy for the treatment of retinal diseases: 17 with PDR and eight with idiopathic macular hole (MH). Qualitative evaluation of the MMP-2 and MMP-9 activation status was performed by gelatin zymography and quantitative assay was carried out for vitreous total protein content and alpha(2)M. The proteolytic state of alpha(2)M was evaluated by Western blotting. Although all vitreous samples contained proMMP-2, increased proMMP-9 and active MMP-9 were detected in PDR samples without PRP. In addition, after PRP the proMMP-9 activity was significantly decreased, whereas the proMMP-2 activity was not affected. Enhanced total protein and alpha(2)M concentrations were observed in all vitreous samples from PDR patients with and without previous PRP compared with samples from patients with MH. However, a differential proteolytic state of alpha(2)M, expressed as 180/85-90kDa ratio, was detected among PDR patients with and without PRP treatment. Whereas a low 180/85-90kDa ratio of alpha(2)M in vitreous of PDR patients without PRP was observed, a high proportion of 180kDa subunit was principally detected in PDR with PRP. These results demonstrate that PDR occurs with an enhanced activity of MMP-9 and activation of alpha(2)M by proteinases, which is reversed after PRP. In addition, we suggest that alpha(2)M plays a key role in the control and regulation of the ocular neovascularization involved in the pathogenesis of ischemic retinal diseases such as PDR.