[Treatment of exudative age-related macular degeneration: Consensus of French experts for first-line treatment selection and the importance of long-term risk/benefit ratio]. / Consensus d'experts français sur les critères de choix d'un traitement de 1re intention dans la DMLA néovasculaire et importance du ratio bénéfice/risque à long terme.

Choosing a first-line treatment to optimize long-term outcomes is a major challenge for treating patients with neovascular age-related macular degeneration (AMD). The development of several new molecules makes it critical to identify the relevant factors to consider so as to provide an optimal risk-benefit ratio when initiating a treatment in naïve patients with neovascular AMD. This paper proposes a consensus established with the Delphi method (which includes a gradation in a consensus based on an analysis of the convergence rate of answers) to provide criteria that guide the ophthalmologist's decision for treatment initiation and follow-up in neovascular AMD patients. Fourteen questions were submitted to 93 French retina experts. Thirteen (93%) of the questions reached a consensus (≥50% of answers consensual). The criteria recommended to take into account were both efficacy and onset of action of the molecules, their safety, and the ability to decrease injection frequency. The primary criterion of expected efficacy of a molecule is a combination of the gain in visual acuity and resorption of retinal fluid. With regard to safety, experts recommend tighter follow-up for molecules currently in development, and at every scheduled visit, patients should be screened to identify early any potential adverse effects such as intraocular inflammation, retinal vasculitis or vascular occlusion. Experts also emphasize the importance of the packaging of the biological, with a preference toward prefilled syringes. Injection frequency is a key factor, and the authors recommended aiming for a maximal injection interval of 12 to 16 weeks. The stability of that maximum interval is also an important factor to consider in treatment selection.

Elastokine-mediated up-regulation of MT1-MMP is triggered by nitric oxide in endothelial cells.

Membrane-type I matrix metalloproteinase (MT1-MMP) has been previously reported to be up-regulated in human microvascular endothelial cell-1 line (HMEC) by elastin-derived peptides (elastokines). The aim of the present study was to identify the signaling pathways responsible for this effect. We showed that elastokines such as (VGVAPG)(3) peptide and kappa elastin induced nitric oxide (NO) production in a time-, concentration- and receptor-dependent manner as it could be abolished by lactose and a receptor-derived competitive peptide. As evidenced by the use of NO synthase inhibitors, elastokine-mediated up-regulation of MT1-MMP and pseudotube formation on Matrigel required NO production through activation of the PI(3)-kinase/Akt/NO synthase and NO/cGMP/Erk1/2 pathways. Elastokines induced both PI(3)-kinase p110gamma sub-unit, Akt and Erk1/2 activation, as shown by a transient increase in phospho-Akt and phospho-Erk1/2, reaching a maximum after 5 and 15 min incubation, respectively. Inhibitors of PI(3)-kinase and MEK1/2 suppressed elastokine-mediated MT1-MMP expression at both the mRNA and protein levels, and decreased the ability of elastokines to accelerate pseudotube formation. Besides, elastokines mediated a time- and concentration-dependent increase of cGMP, suggesting a link between NO and MT1-MMP expression. This was validated by the use of a guanylyl cyclase inhibitor, a NO donor and a cGMP analog. The guanylyl cyclase inhibitor abolished the stimulatory effect of elastokines on MT1-MMP expression. Inversely, the cGMP analog, mimicked the effect of both elastokines and NO donor in a concentration- and time-dependent manner. Overall, our results demonstrated that such elastokine properties through NO and MT1-MMP may be of importance in the context of tumour progression.

A peptide of the alpha 3(IV) chain of type IV collagen modulates stimulated neutrophil function via activation of cAMP-dependent protein kinase and Ser/Thr protein phosphatase.

Previous reports from our laboratories showed that type IV collagen from anterior lens capsule (ALC) inhibited stimulated neutrophil function. This property was shown to reside in the region comprising residues 185-203 of the non-collagenous domain (NC1) of the alpha 3(IV) chain. We also reported that ALC-type IV collagen or the synthetic alpha 3(IV) 185-203 peptide, induced a rise in intracellular cAMP which persisted for up to 60 minutes. In the present work we extend our previous studies on signal transduction by alpha 3(IV) 185-203 and we provide new data showing the involvement of cAMP-dependent PKA and protein phosphatases. The data also show that the alpha 3(IV) peptide triggered a rise in intracellular calcium that was dependent on phospholipase C activation. Inhibitors of the Ca(2+)/calmodulin system suppressed both the alpha 3(IV) 185-203 peptide-induced cAMP increase and the inhibitory activity of the peptide on f-Met-Leu-Phe triggered O(2)(-) generation. When alpha 3(IV) 185-203 peptide-induced calcium mobilization was blocked by U-73122, an inhibitor of phospholipase C activation, or by BAPTA/AM, a chelator of intracellular calcium, the inhibitory effect of the peptide on PMA-triggered O(2)(-) production was also abolished. These findings provide evidence that signal transduction by the alpha 3(IV) peptide occurs via pathways which involve calcium. Indeed, the cAMP increase was shown to be mediated by adenosine and adenosine A2 receptors and required calcium elevation, since adenosine deaminase, theophilline, dimethylpropargylxanthine, trifluoperazine or autocamtide-2 related inhibitory peptide, suppressed the activity of the alpha 3(IV) peptide. The inhibitory effect of the peptide on f-Met-Leu-Phe-induced O(2)(-) generation was slightly affected by 1 microM KT5720 or H89, two inhibitors of cAMP-dependent PKA, but was completely suppressed by 10 nM calyculin A or 10 microM okadaic acid, two inhibitors of ser/thr phosphatases. These results suggest that Ser/Thr protein phosphatases and/or cAMP-dependent PKA are involved in signal transduction by the alpha 3(IV) 185-203 peptide and is consistent with the concept that adenosine receptor occupancy modulates neutrophil function.

[Mixed retinal thrombosis in a patient carrying prothrombin gene mutation in a homozygote state]. / Thrombose mixte rétinienne chez un patient porteur d'une mutation du gène de la prothrombine, à l'état homozygote.

We reported a case of a thrombosis of the retinal and central artery and vein in a 44-year-old patient, with high-grade T-cell lymphoma. Cardiovascular family history and a medical history of cerebral ischemia caused by in situ fibrinolysis, led to perform thorough hematologic and genetic examinations. These disclosed a prothrombin gene G 20210 a variant in a homozygous state. In a heterozygous state, this mutation leads to an increase in plasma prothrombin rate of the order of 30%. Therefore, it is considered to be a major risk factor for venous thrombotic disease. Otherwise, acute leukemia or non-Hodgkin's lymphoma may induce thrombosis of retinal artery and vein by means of an optic nerve infiltration, as well as beta-thalassemia, ocular trauma and retrobulbar anesthesia. Retinal central artery and vein are seldom both involved; whereas occlusions of their branches are more frequent.

Retinal detachment after clear lens extraction for high myopia: seven-year follow-up.

OBJECTIVE: To prospectively evaluate the incidence of complications, particularly retinal detachment, 7 years after clear lens extraction (CLE) for myopia greater than -12 diopters (D). DESIGN: Extended follow-up of noncomparative case series. PARTICIPANTS: Fifty-two eyes of 30 patients with preoperative myopia greater than -12 D, best-corrected visual acuity (BCVA) of 20/100 or better, and intolerance of contact lenses. INTERVENTION: Patients with lattice degeneration, retinal tear, or hole underwent photocoagulation before CLE. The authors performed phacoemulsification through a 3.2-mm-wide incision using primary irrigation and aspiration, widened the incision to 6.5 mm, and implanted a one-piece polymethyl methacrylate intraocular lens (IOL). MAIN OUTCOME MEASURES: The BCVA, uncorrected visual acuity (UCVA), stability of spherical equivalent (SE), neodymium:YAG (Nd:YAG) capsulotomy rate, and complications (especially retinal detachment). RESULTS: At 7 years, the SEs of 29 eyes (59.1%) were within +/-1.0 D of emmetropia and 42 eyes (85.7%) were within +/-2.0 D. Mean SE was -1.01 D (+/-0.94). At 7 years, mean UCVA was 20/80 compared with 20/66 at 1 year. BCVA and UCVA were better in eyes with open capsules versus intact capsules. During the 7 years, 30 eyes (61.2%) required capsulotomy for opacification. Mean time for capsulotomy was 48.4 months after CLE. The authors performed ten argon laser retinal treatments after surgery, with all but one in the first postoperative year. The overall incidence of posterior vitreous detachment was 16.3%. The incidence of retinal detachment during the 7 years was 4 of 49 eyes, or 8.1% (vs. 2.0% at 4 years). One patient had bilateral retinal detachments. CONCLUSION: Despite advances in surgical technique, retinal detachment remains a major concern after CLE for high myopia. In the authors' series, the incidence of retinal detachment after CLE was nearly double that estimated for persons with myopia greater than -10 D who do not undergo surgery. Although CLE has advantages, including rapid and predictable visual rehabilitation, stable refraction, the ability to replace the IOL, and often superb optical quality with no irregular astigmatism, it is invasive and can result in severe vision loss. Long and continuous follow-up of the outcomes of CLE for high myopia is absolutely necessary before the authors can consider CLE as a routine option for patients with high myopia.

Conjunctival epithelial neoplasias in organ transplant patients receiving cyclosporine therapy.

PURPOSE: To report two cases of conjunctival epithelial neoplasias occurring after long-term systemic cyclosporine therapy in organ transplant recipients. METHODS: Case report. Each patient underwent an excision of an extensive limbal conjunctival lesion, followed by a histopathologic analysis. RESULTS: Histopathologic examination results revealed a carcinoma in situ and a squamous cell carcinoma in patients 1 and 2, respectively. Recurrence occurred in patient 1, who needed topical mitomycin C 0.02% treatment. No recurrence was observed in patient 2 after a follow-up of 24 months. CONCLUSION: To our knowledge, these are the first reported cases of its kind after longterm systemic cyclosporine therapy. Further studies will be needed to determine the exact role of cyclosporine in the induction of conjunctival epithelial neoplasias and the need for regular ophthalmologic examination of transplant recipients.

Penetration of piperacillin into the vitreous after intravenous administration.

PURPOSE: Penetration of piperacillin into the vitreous cavity after intravenous administration was investigated in humans. METHODS: Forty-five eyes undergoing vitrectomy between November 1993 and December 1994 were included. Each patient received a single intravenous dose of piperacillin 4 g 2 hours before ocular incision. A 0.2-mL vitreous sample was aspired at the beginning of vitrectomy, a blood sample was obtained, and piperacillin level was assessed. RESULTS: There were no detectable drug concentrations in 25 eyes. Mean vitreous drug concentration in the remaining evaluable eyes (n = 14) was 2.33 microg/mL (+/-0.76). We divided samples into two groups: 23 uninflamed (Group 1) and 16 inflamed (Group 2) eyes. Mean vitreous drug concentration was 0.42 microg/mL in Group 1 and 4.95 microg/mL in Group 2 (P < 0.2). Piperacillin concentration was higher than the minimum inhibitory concentration for gram-positive bacteria in 13% of uninflamed and 69% of inflamed eyes (P < 0.001). CONCLUSION: Studies show that intravenously administered piperacillin can penetrate the vitreous cavity in rabbits. Our study suggests that a single dose of piperacillin can produce intravitreal concentrations sufficient to kill gram-positive bacteria in inflamed eyes. The poor intraocular penetration of systemically administered piperacillin in uninflamed eyes raises questions about its usefulness as a prophylactic agent in ophthalmic surgery.

Clear lensectomy and implantation of a low-power posterior chamber intraocular lens for correction of high myopia: a four-year follow-up.

PURPOSE: To evaluate the 4-year postoperative outcomes of patients who are highly myopic who underwent clear lensectomy via phacoemulsification and low power posterior chamber intraocular lens implantation. METHODS: The authors performed surgery in 52 eyes of 30 patients in which prophylactic retinal treatment, clear lensectomy, and posterior chamber intraocular lens implantation were used to treat high myopia of 12 diopters (D) or greater. A total of 49 eyes of 28 patients were evaluated at the 4-year postoperative timeframe. Visual acuity, complications, and refractive stability were assessed. RESULTS: The incidence of retinal detachment through 4 years was 1.9%. No new macular complications were observed. Two patients had posterior vitreous detachment without clinical impact between 1 and 4 years after surgery. The incidence of neodymium:YAG (Nd:YAG) capsulotomy was 36.7%. The mean postoperative spherical equivalent was -0.92 D. Four patients had a myopic shift of 0.50 D to 1.00 D from the 1- to 4-year timeframe. Corrected visual acuity of 20/40 or better was achieved in 82% of eyes that had undergone Nd:YAG capsulotomy versus 56% of untreated eyes. Uncorrected visual acuity of 20/100 or better was achieved in 82% of eyes treated with the Nd:YAG laser versus 62% of untreated eyes. CONCLUSION: Visual acuity and refractive outcomes with clear lensectomy are favorable. Retinal detachment remains the major concern of this procedure. Continuous follow-up of these patients is necessary.

[Value of serodiagnosis of Lyme disease in the evaluation of uveitis]. / Intérêt du sérodiagnostic de la maladie de Lyme dans le bilan des uvéites.

PURPOSE: This study was designed to assess results of Lyme serology among all the specific tests routinely performed for exploring uveitis. METHODS: Sixty-seven patients examined for uveitis had a serological diagnosis of Lyme's disease with haemagglutination test and ELISA IgG test. This group included 34 patients with unclassified uveitis. Thirty-seven healty individuals served as control subjects. RESULTS: There was no statistical difference between the three groups in terms of positive serological diagnosis occurrence: control subjects (13.5%), patients with classified uveitis (12.1%) and patients with unclassified uveitis (11.8%). CONCLUSION: It appears to be more adequate to reserve this serological test for Lyme's disease for patients who have a suggestive history or additional symptoms.

[Infectious crystalline keratopathy occurring after penetrating keratoplasty]. / Kératopathie cristalline infectieuse survenue après kératoplastie transfixiante.

Infectious crystalline keratopathy is a chronic corneal infection, characterized by interlamellar opacities that are shaped like crystal formations. In the majority of cases, Streptococcus viridans is cultured. We report the case of a 74 year old man, presenting with corneal infection in a donor graft after penetrating keratoplasty. A Streptococcus sanguis was isolated. The clinical response to antibiotics was poor, with a slow and inexerable progression, leading to possible corneal regrafting.

Clear lensectomy and implantation of low-power posterior chamber intraocular lens for the correction of high myopia.

BACKGROUND: Although a variety of surgical procedures to treat high myopia have been studied, no consensus exists on the optimum procedure. Clear lensectomy with implantation of a posterior chamber intraocular lens has been regarded as risky, due to the higher incidence of retinal detachment in highly myopic eyes. METHODS: The authors performed surgery and evaluation over 1 year in 52 eyes in which prophylactic retinal treatment, clear lensectomy, and posterior chamber intraocular lens implantation were used to treat high myopia of 12 diopters (D) or greater. RESULTS: Before lens extraction, 31 eyes underwent argon laser photocoagulation. Over the 1-year period, three additional eyes were treated, and six eyes that had been treated preoperatively received additional treatment. No cystoid macular edema, retinal detachment, or persistent corneal edema was observed in this series. At 1 year, 88.5% of the group achieved corrected visual acuity of 20/40 or better, compared with 75% preoperatively. Uncorrected visual acuity of 20/100 or better was achieved by 84.6% of the group. The mean postoperative spherical equivalent was -0.86 +/- 0.84 D. CONCLUSION: The refractive objectives were achieved. Complications reported previously with clear lensectomy were not experienced in this group. The low incidence of complications can be attributed to the short follow-up and probably in part to the prophylactic retinal treatment, combined with the phacoemulsification procedure for lens extraction. Longer follow-up is needed to fully assess the complications. Properly randomized prospective clinical trials will be able to fully assess the benefits and risks of prophylactic retinal treatment and clear lens extraction with posterior intraocular lens implantation. This series can help in evaluating this surgical procedure.

[Preventive treatment of herpetic keratitis with acyclovir tablets]. / Traitement préventif des kératites herpétiques par l'acyclovir en comprimés.

Although several drugs are available to treat superficial herpes simplex keratitis, viral latency and recurrences represent clinical challenges that have been inadequately addressed by current topical antiviral agents. One hundred and ninety patients with previous herpes simplex keratitis were entered in an open study to evaluate the efficacy of the prophylactic therapy of recurrence with Acyclovir (200 mg) four times daily for 1 month to 24 months. Forty patients were treated because of frequently recurring herpetic keratitis; 36 were treated during a short period because of known risk factors; 23 were treated after ocular surgery which needed topical corticosteroid therapy in the postoperative period and 91 patients were treated after penetrating keratoplasty for herpetic keratitis. The results of this study indicate that oral Acyclovir significantly lowered the incidence of recurrences of herpetic keratitis in selected patients.

[Exfoliative syndrome and cataract surgery]. / Syndrome exfoliatif et chirurgie de la cataracte.

In the present prospective study, we compared the results of cataract surgery in two groups with or without exfoliation syndrome; 210 eyes were studied. The preoperative pupillary dilatation was smaller in the group with exfoliation syndrome (SE). We noticed a higher incidence of complications during planned extracapsular cataract extraction in patients with SE. A pupillary diameter smaller than 6 mm increases the incidence of capsulozonular rupture (22.5%) in these patients. After surgery, an inflammatory reaction and a transient increase in intraocular pressure were more frequent and the visual results were less favourable in the group with SE. The exfoliation syndrome is a major risk factor for cataract surgery. We recommend extracapsular extraction associated with a sector iridectomy when the pupillary diameter measures less than 6 mm.