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Purpose: We describe the first case of a novel surgical technique of mini-invasive corneal neurotization (MICORNE) using the lateral antebrachial cutaneous nerve as a graft nerve and the contralateral supraorbital nerve as a donor nerve in a herpetic patient with a neurotrophic keratopathy (NK)., Methods: A MICORNE procedure was performed in a 32-year-old man with a 5-year history of herpes simplex virus (HSV)-related NK in the right eye (RE). Visual acuity and corneal sensation were assessed over 9 months of follow-up. HSV-1 and HSV-2 genomes were screened preoperatively and postoperatively in the patient's tears using the quantitative polymerase chain reaction technique. A high does of the oral antiviral prophylaxis was prescribed during the follow-up., Results: Preoperative best-corrected visual acuity was 20/200 in the RE. A Cochet-Bonnet esthesiometer revealed complete corneal anesthesia (<5 mm ie, >15.9 g/mm) in all quadrants in a scarred and neovascularized cornea. Twelve months after the procedure, the visual acuity of the RE was 20/80 and corneal sensitivity had increased to 40 mm, that is, 0.8 g/mm (superior quadrant), 35 mm, that is, 1 g/mm (inferior quadrant), 40 mm (temporal quadrant), 35 mm, that is, 1 g/mm (nasal quadrant), and 40 mm (centrally). We observed no clinical recurrence of herpes, and HSV was not detected in tears during the follow-up period., Conclusions: We report the first case of MICORNE, a novel surgical technique of corneal neurotization in a herpetic patient with NK. Despite the potential risk of viral recurrence, our patient showed dramatic improvement in corneal sensation and visual acuity.

Recurrent herpes simplex keratitis (HSK) is a leading infectious cause of blindness in industrialized countries. Antiviral prophylaxis (AVP) may fail to prevent recurrence of HSK due to viral resistance, inadequate dosing, or poor patient compliance. In this prospective multicenter study, we enrolled immunocompetent patients with recurrent HSK despite AVP. Ocular samples were tested by PCR for herpes simplex virus 1 (HSV-1). HSV-1 drug resistance was assessed with a genotypic assay based on UL23 and UL30 gene sequencing. After curative full dose valacyclovir (VACV) treatment was started, peak and trough acyclovir (ACV) plasma concentrations were measured, and patient compliance to AVP was assessed with a questionnaire. The study sample was comprised of 43 patients. Six (14%) patients were positive for HSV-1 using PCR, of whom 5 (83%) harbored genotypically ACV-resistant (ACV R ) virus, due to mutations in UL23 (n = 4) or UL30 (n = 1). Disease duration was statistically significantly longer in patients with viral resistance compared to other HSK patients [35.5 ± 23.4 years (range, 6.8-68.4 years) versus 11.1 ± 12.3 years (range, 0.8-56.3 year) respectively; Mann-Whitney p = 0.01)]. While patients were treated with full dose VACV, trough ACV plasma concentrations were below the threshold for ACV sensitivity in 9.5% of cases, and compliance was poor in 5.3% of cases. To summarize, HSV-1 resistance to ACV seems to be a significant cause of failure of prophylaxis in patients with HSK and is associated with longer disease duration. Most PCR-positive samples contained genotypically ACV R virus and identification may aid in adapting treatment. Incomplete 24-h drug coverage may also explain some cases of failure of prophylaxis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the feasibility of robot-assisted simulated cataract surgery., Setting: Institut de Recherche Contre les Cancers de l'Appareil Digestif, European Institute of Telesurgery, and Strasbourg University Hospital, Strasbourg, France., Design: Experimental study., Methods: Cataract surgeries were performed on a Kitaro cataract wet-lab training system simultaneously using the Da Vinci Xi robotic surgical system and the Whitestar Signature phacoemulsification system. For each procedure, the duration and successful completion of the surgery with or without ocular complications were assessed., Results: Procedures were successfully performed on 25 lens nuclei. The feasibility of robot-assisted simulated cataract surgery was confirmed. The robotic surgical system provided the intraocular dexterity and operative field visualization necessary to perform the main steps of the phacoemulsification procedure; that is, corneal incisions, capsulorhexis, grooving, cracking, quadrant removal, and irrigation/aspiration of the ophthalmic viscosurgical device (OVD). The intervention of a second surgeon was required for the intraocular injections of OVD, balanced salt solution, and intraocular lenses. The mean operative time was 26.44 minutes ± 5.15 (SD). All lens nuclei were removed. Inadvertent enlargement of the main corneal incision caused by the phaco handpiece was observed in 2 cases., Conclusion: Experimental robot-assisted cataract surgery was technically feasible using the new robotic surgical system combined with a phacoemulsification machine., (Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Background: Congenital cataract is of particular interest because of the variability of etiologies and the inflammatory reaction that are often observed. The aim of the study was to describe intraocular levels of various inflammation-related cytokines of patients with congenital cataract and to study their correlations with clinical determinants., Methods: We followed a cohort of 18 patients (18 eyes) with congenital cataract from a University hospital and measured levels of various inflammation-related cytokines in the aqueous humor of patients with congenital cataract, and compared these levels to those observed in a control group (patients with senile cataract) using multiplex immunoassay. Correlation analysis was used to study the possible correlation between intraocular levels of cytokines and clinical determinants., Results: Compared with the control group, the group with congenital cataract showed clear and significantly elevated concentrations of inflammatory markers (IL-1β, IL-15, IFN-γ, IL-12, IL-6, IL-5, IL-9, MIP-1α, MCP-1 and IP-10). Postoperative intraocular inflammation and opacification of the posterior capsule seemed to be correlated with preoperative IL-1β, TNF-α and IL-6 levels., Conclusions: An inflammatory condition may occur in eyes with congenital cataract. The cytokine profiles are really different than those observed in senile cataract. Moreover, cytokines levels may be of interest to predict posterior capsule opacification and to complete the etiological workup.

A growing number of receptors, often associated with the innate immune response, are being identified as targets for bacterial toxins of the beta-stranded pore-forming family. These findings raise the new question of whether the receptors are activated or merely used as docking points facilitating the formation of a pore. To elucidate whether the Staphylococcus aureus Panton-Valentine leukocidin and the leukotoxin HlgC/HlgB act through the C5a receptor (C5aR) as agonists, antagonists or differ from the C5a complement-derived peptide, their activity is explored on C5aR-expressing cells. Both leukotoxins equally bound C5aR in neutrophils and in stable transfected U937 cells and initiated mobilization of intracellular Ca(2+) . HlgC/HlgB requires the presence of robust intracellular acidic Ca(2+) stores in order to evoke a rise in free [Ca(2+) ]i , while the LukS-PV/LukF-PV directly altered reticular Ca(2+) stores. Intracellular target specificity is conferred by the F-subunit associated to the S-subunit binding the receptor. Furthermore, internalization of the two leukotoxin components (S- and F-subunits) associated to C5aR is required for the initiation of [Ca(2+) ]i mobilization. Electrophysiological recordings on living cells demonstrated that LukS-PV/LukF-PV does not alter the membrane resistance of C5aR-expressing cells. The present observations suggest that part of the pore-forming process occurs in distinct intracellular compartments rather than at the plasma membrane., (© 2015 John Wiley & Sons Ltd.)

Uveitis is a potentially blinding inflammatory disease. Thirty to 50% of uveitis cases are considered idiopathic. The present study sought to determine the intraocular cytokine patterns in the different etiological types of uveitis in order to better understand their immunological regulation and to determine whether the cytokine pattern may be a useful diagnostic tool. From a multicenter institutional prospective study, the clinical and biological data from patients with uveitis of various etiologies, determined after a complete workup, were compared with those from a control group of cataract patients. A multiplex assay was used to assess the profiles of 27 cytokines and chemokines in aqueous humor samples from these patients. In total, 62 patients with infectious or noninfectious uveitis and 88 controls were included. After a complete workup, the cause of uveitis remained unknown in 25 patients (40% idiopathic uveitis). Interleukin 1β (IL-1β) levels were markedly increased in viral uveitis, as were IL-10 levels, whereas IL-17A levels were augmented in toxoplasmic uveitis. Based on the cytokine pattern, the patients were reassigned to specific groups. At the end of the study, the diagnosis of idiopathic uveitis was still valid in only 11 patients (18%). The observation that some markers are specific to certain diseases enables a better understanding of the disease pathogenesis and paves the way for new diagnostic methods aimed to identify inflammatory markers, which may perhaps be targeted by therapy., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Retinal lesions or other ocular manifestations are serious consequences of infection with the protozoan parasite Toxoplasma gondii. Whilst classically considered a consequence of congenital transmission, recent screening studies estimated that 2% of T. gondii seropositive persons in Europe and North America have retinal lesions, most of them persisting unnoticed. The situation is more dramatic in South America, probably due to the predominance of virulent strains. Some of these strains seem to exhibit ocular or neuronal tropism and are responsible for severe ocular lesions. Despite the medical importance, the physiopathological mechanisms have only recently begun to be elucidated. The particular immune-privileged situation in the eye has to be considered. Studies on French patients showed low or undetectable ocular parasite loads, but a clear Th1/Th17 type immune reaction. Suitable mouse models have appeared in the last few years. Using such a model, IL-17A proved to impair parasite control and induce pathology. In contrast, in South American patients, the parasite seems to be much less efficiently controlled through a Th2 type or suppressive immune response that favors parasite replication. Finally, several host genetic markers controlling immune response factors have been associated with ocular involvement of T. gondii infection, mainly in South America., (Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the impact of recurrent unilateral herpetic keratitis (HK) on the tear secretion of the unaffected fellow eye., Design: Prospective, noninterventional study., Participants and Controls: Thirty-five patients with a history of recurrent unilateral HK (clinically quiescent for at least 3 months) (HK group) and 35 patients who were age- and sex-matched with no history of corneal disease (control group)., Methods: Tear osmolarity, tear instability (tear break-up time [TBUT]), tear reflex (Schirmer's I test), and central corneal sensitivity with the Cochet-Bonnet esthesiometer (Luneau, France) were measured in the HK and control groups., Main Outcome Measures: Tear osmolarity, TBUT, Schirmer's I, and central corneal sensitivity were compared between the affected and unaffected eyes of the HK and control groups., Results: Tear osmolarity and tear secretion reflex were similar between the affected and unaffected eyes of the HK group. Corneal sensitivity and TBUT were statistically lower in the affected eyes compared with the unaffected eyes in the HK group (P = 0.001 and P<0.001, respectively). The central corneal sensitivity of unaffected eyes in the HK group was not significantly different from that in the control group (P>0.05). The tear stability and tear secretion reflex were decreased and tear osmolarity was increased in the unaffected eyes of the HK group compared with the control group (P<0.05, all cases). The difference between unaffected and control eyes varied according to the type of HK. All 4 tests were modified in patients with neurotrophic keratitis (KN). In the keratouveitis subgroup, only corneal sensitivity was normal, whereas Schirmer's I results were also normal in patients with archipelago keratitis. Tear osmolarity was consistently affected in both eyes of herpetic patients., Conclusions: Tear function is impaired in the unaffected eyes of patients with unilateral recurrent HK, even when the disease is apparently quiescent. The higher severity of results in the unaffected fellow eye of patients with KN in comparison with other herpes subgroups suggests that recurrent HK induces a reduction in the afferent pathways of the tear secretion reflex from the affected eye, leading to tear dysfunction in the unaffected eye., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the results and safety of sutureless intrascleral haptic fixation in traumatized eyes and to compare this procedure with retropupillary iris-claw intraocular lens (IOL) fixation., Setting: University Hospital of Strasbourg, Strasbourg, France., Design: Interventional case series., Methods: Patients with traumatic cataract and severely damaged capsular bags were divided into 2 groups (Group 1: intrascleral IOLs [Acrysof MN60 AC]; Group 2: retropupillary iris-claw IOLs [Verisyse]). The main outcome was the final visual acuity. The surgically induced astigmatism (SIA) was calculated by the vectorial method., Results: Twenty-six eyes of 23 patients were studied, 8 eyes in Group 1 and 18 eyes in Group 2. The mean follow-up was 14 months. There was no difference in corrected distance visual acuity (CDVA) at the time of the surgery (P>.05). The mean CDVA (logMAR) was 1.68 ± 1.15 (SD) preoperatively and 0.55 ± 0.9 postoperatively in Group 1 (P = .03) and 1.11 ± 1.13 and 0.32 ± 0.47, respectively, in Group 2 (P = .003). The final CDVA was not different between groups (P>.05). The mean SIA was 1.91 ± 1.66 diopters (D) in Group 1 and 2.74 ± 1.92 D in Group 2 (P>.05). No intraoperative complications occurred in Group 2; a haptic broke in Group 1. Macular edema occurred in both groups., Conclusions: Sutureless intrascleral IOLs corrected posttraumatic aphakia. The SIA was comparable between groups. This procedure should be considered after trauma when other implantation techniques are not possible., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy of intravitreal administration of linezolid (LZD) in a rabbit model of Staphylococcus aureus endophthalmitis., Methods: Of 40 rabbits studied, 36 of them received 10(2) colony-forming units (CFU) of S. aureus in their right eye before being randomly assigned to the following groups: four groups of 8 animals received 24 hours after the bacterial inoculation, 1, 10, 30 mg of LZD (LZD 1, LZD 10, and LZD 30) or 1 mg of vancomycin (V1), respectively. Four other animals had a sham injection in their infected eye. The 4 remaining animals were used as negative controls. Clinical, bacterial, and histologic assessments were conducted at different endpoints. Animals were euthanized at day 8. The safety profile of intravitreal LZD was assessed by electroretinography in 5 more animals by comparing the recordings in eyes injected with 30 mg of LZD and contralateral control eyes injected with a solution of sterile saline water., Results: At day 5, the mean inflammatory clinical scores of Nussenblatt were 7.0 ± 1.0, 3.6 ± 0.7, and 3.1 ± 0.8, in the LZD 1, LZD 10, and LZD 30 groups and 3.4 ± 1.7 and 7.5 ± 0 in the V1 and BSS+ groups, respectively (P < 0.05, ANOVA). The corresponding mean bacterial counts in the vitreous (log 10 CFU/mL) were 6.2 ± 6.5, 3.5 ± 3.8, 0, 3.8 ± 4.2, and 7.8 ± 4.9, respectively (P < 0.05, ANOVA). A 30 mg dose of LZD sterilized all the eyes at day 5 and displayed the lowest (best) histologic score (1.5 ± 0.6). Residual LZD concentrations 24 hours after the administration were between 0.1 and 7.2 mg/L LZD 30 group. The half-time of linezolid in the vitreous was 2 hours. There were no differences in the electroretinogram recordings between control eyes and eyes injected with 30 mg of linezolid at days 1 and 14 after the intravitreal injection., Conclusions: This is the first evidence of the effectiveness of linezolid for the treatment of experimental staphylococcal endophthalmitis. High ocular concentrations of LZD were needed to obtain a satisfactory bactericidal effect. Linezolid displayed a concentration-dependent killing activity in the eye. Such doses of intravitreal linezolid appeared to be safe for the retinal function.

The increasing use of immunosuppressive (IS) drugs in transplants or in systemic diseases, implies a long period of treatment and to be aware of possible side effects. These drugs can be used alone or in combination with steroids. This review deals with the issue of ocular side effects of the most used IS drugs, including steroids. Data were collected from Medline using Pubmed software. We first describe specific complication of each drug and then conclude on major common toxicity represented by opportunistic infections and induced cancers., (2010 Société Française de Pharmacologie et de Thérapeutique.)

Red eye in children is a common consultation purpose. Mostly benign, this sign may also cause visual impairment. We differentiate three kinds of red eye: localised, diffused and perikeratic injection. The last one must be recognized because of its association with severe ocular diseases. Diagnosis must be sure and treatment has to be efficient to not pertubate childrens visual development. Unfortunately, physical examination on children is not always easy. Consultation with an ophthalmologist is justified if a doubt remains, in case of chronic pathology or resistance to first intention treatment.

Background: It is now possible to treat ocular surface disorders by means of amniotic membrane transplantation. We performed a study to determine the efficacy of this technique in the treatment of severe Acanthamoeba keratitis., Methods: We studied six patients with severe, painful, nonhealing Acanthamoeba keratitis who underwent one or two amniotic membrane transplantation procedures between February 2001 and January 2003. Histopathological analysis of the corneal buttons was performed in four cases., Results: Eight amniotic membrane transplantation procedures were performed. The mean length of follow-up was 14 (range 3-21) months. The mean interval between institution of medical treatment and the procedure was 3.6 months. All patients had progressive stromal lesions caused by an inflammatory reaction. Complete reepithelialization occurred in four cases, and partial healing in two cases. Ocular inflammation and tissue destruction were decreased in all cases, pain was lessened in five cases, and corneal neovascularization was decreased in four cases. No postoperative complications were observed. Amniotic membrane was observed under dysplastic corneal epithelium on histologic examination., Interpretation: Amniotic membrane transplantation may be a safe and effective treatment of severe Acanthamoeba keratitis, particularly during the inflammation phase. It may permit penetrating keratoplasty to be delayed.

Purpose: The aim of this study was to investigate whether cultured human corneal fibroblasts express functional chemokine CXCR4 receptors on their cell surface and to determine the presence of its specific ligand, SDF-1 (CXCL12), in human corneal fibroblasts., Methods: Human corneal fibroblast cultures were obtained using human donor corneas. CXCR4 receptors were characterized using binding studies and autoradiography with [125I]SDF-1. The functionality of CXCR4 receptors was assessed by intracellular calcium measurement using a dynamic imaging microscopy system. CXCR4 and SDF-1 mRNA were detected in human corneal fibroblasts using reverse transcriptase polymerase chain reaction (RT-PCR). The CXCR4 protein was detected by western blot analysis., Results: [125I]SDF-1 specifically bound to cultured corneal fibroblasts with a KD value of 8.3+/-1.2 nM. The presence of CXCR4 was confirmed by autoradiography of the radioligand on slices of corneal stroma. SDF-1 induced a rapid and transient intracellular calcium increase in cultured corneal fibroblasts that was blocked by the specific antagonist bicyclam. Moreover, a 48 kDa protein was detected by western blot analysis of corneal fibroblast extracts, using a specific CXCR4 polyclonal antibody. RT-PCR showed the expression of both CXCR4 and SDF-1 mRNAs in human corneal fibroblasts., Conclusions: These results indicate for the first time that cultured human corneal fibroblasts express the chemokine receptors CXCR4 and its ligand SDF-1. This latter might exert physiological effects on the cornea and could be involved in pathological conditions such as corneal angiogenesis.

Purpose: The purpose of the study was to investigate whether cultured human keratocytes express the neurotensin receptors (NTR1, NTR2, and NTR3), to determine the presence of neurotensin (NT) in keratocytes, and to assess the influence of NT on these cells., Methods: Human keratocytes were cultured in medium treated with various concentrations (10(-7)-10(-9) M) of JMV449 (a weakly degradable NT agonist). Cell proliferation and viability were analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay. Apoptosis was studied by nucleus labeling with a fluorescent dye and cold light fluorometry. NT, NTR1, NTR2, and NTR3 mRNA were detected in human keratocytes by means of reverse transcriptase-polymerase chain reaction (RT-PCR). NTR1 protein was detected by Western blot analysis. Functionality of NTR1 was assessed by intracellular calcium ([Ca2+]i) measurement with a dynamic imaging microscopy system., Results: RT-PCR and Western blot analysis showed the expression of the NTR1 (mRNA and protein) and NTR3 mRNA in human corneal keratocytes. NT and NTR2 mRNA were undetectable. JMV449 induced a rapid and transient [Ca2+]i increase in human corneal keratocytes that was blocked by the specific antagonist SR48692. JMV449 significantly increased cell proliferation and viability after 72, 96, and 120 hours of culture, with a maximum effect at 10(-7) M (P < 0.005). Finally, JMV449 decreased keratocyte apoptosis, whatever the concentration used (P < 0.005)., Conclusions: These results indicate that cultured human keratocytes express NTR1 and NTR3 and that NT may exert physiological effects on cornea such as regulation of keratocyte proliferation and apoptosis.