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Biomedical subjects

Laurent Kodjikian

Publications and source records attributed to Laurent Kodjikian.

At least 19 recordsLinked to original sources

Visual function in human ocular toxoplasmosis.

AIM: To assess functional impairment in terms of visual acuity reduction and visual field defects in inactive ocular toxoplasmosis. METHODS: 61 patients with known ocular toxoplasmosis in a quiescent state were included in this prospective, cross-sectional study. A complete ophthalmic examination, retinal photodocumentation and standard automated perimetry (Octopus perimeter, program G2) were performed. Visual acuity was classified on the basis of the World Health Organization definition of visual impairment and blindness: normal (> or =20/25), mild (20/25 to 20/60), moderate (20/60 to 20/400) and severe (<20/400). Visual field damage was correspondingly graded as mild (mean defect <4 dB), moderate (mean defect 4-12 dB) or severe (mean defect >12 dB). RESULTS: 8 (13%) patients presented with bilateral ocular toxoplasmosis. Thus, a total of 69 eyes was evaluated. Visual field damage was encountered in 65 (94%) eyes, whereas only 28 (41%) eyes had reduced visual acuity, showing perimetric findings to be more sensitive in detecting chorioretinal damage (p<0.001). Correlation with the clinical localisation of chorioretinal scars was better for visual field (in 70% of the instances) than for visual acuity (33%). Moderate to severe functional impairment was registered in 65.2% for visual field, and in 27.5% for visual acuity. CONCLUSION: In its quiescent stage, ocular toxoplasmosis was associated with permanent visual field defects in >94% of the eyes studied. Hence, standard automated perimetry may better reflect the functional damage encountered by ocular toxoplasmosis than visual acuity.

Adolescent↗

Preparation of vancomycin microparticles: importance of preparation parameters.

The aim of the present work was to prepare microparticles containing vancomycin for intraocular injection. The primary objective was to guarantee continuous release and keep an intracameral drug concentration above the minimal inhibitory limit for at least 24h, needed in endophthalmitis prophylaxis after cataract surgery. Poly(lactide-co-glycolide) microparticles were prepared using the double emulsion (water-in-oil-in-water) solvent extraction/evaporation method. The influence of preparation parameters on the final microparticles properties was explored in an attempt to control particle sizes, stability, encapsulation rate and vancomycin release profile. Satisfying release profile and stability were obtained, independently of the process. Sizes and encapsulation rate were controlled using an experimental design. Final obtained properties demonstrated that the fabricated particles are suitable for the prophylactic intraocular use in cataract surgery. Further in vitro and in vivo experiments will be conducted to assess efficiency of the entrapped antibacterial and then validate its potential usefulness in prophylaxis.

Chemistry, Pharmaceutical↗

Primary transpupillary thermotherapy for 18 small posterior pole uveal melanomas.

PURPOSE: To evaluate transpupillary thermotherapy (TTT) for the treatment of small uveal melanomas of the posterior pole. DESIGN: Prospective, nonrandomized interventional case series. METHODS: Eighteen patients underwent TTT for small uveal melanomas located in the posterior pole of the eyes. Tumors were between 2.5 and 4 mm in thickness. TTT was performed with a diode laser at 810 nm. Patients had between one and three TTT sessions, with an intensity adapted to the coloration of the fundus impact. Biomicroscopic examination, ultrasonographic measurements, and angiography were performed before and two months, four months, and six months after treatment, then regularly during follow-up. RESULTS: Eight of the 18 tumors regressed and 10 recurred. The one- and two-year metastasis-free survival rates calculated by the Kaplan-Meier method were, respectively, 61.11% to 44.44% (95% confidence interval). Recurrences were managed with enucleation (three patients), proton beam therapy (six), or additional thermotherapy (one). After treatment, visual acuity was maintained or improved for the eight patients with nonrecurrent tumors. Pathologic analysis of the three enucleated eyes revealed scleral invasion. CONCLUSIONS: Despite encouraging initial short-term results obtained with TTT for the management of small choroidal melanomas, the occurrence of severe complications, especially recurrences and insufficient local tumor control, should raise concern about indications for primary TTT given as isolated treatment for small melanomas of the posterior pole.

Adult↗

Combined pars plana phacofragmentation, vitrectomy, and Artisan lens implantation for traumatic subluxated cataracts.

PURPOSE: To report on the outcome of combined pars plana phacofragmentation, vitrectomy, and Artisan lens implantation in the management of subluxated cataracts. METHODS: This prospective, interventional, nonrandomized case series included nine eyes of seven consecutive adult patients with traumatic lens subluxation. Pre- and postoperative data (complete manifest refraction, best spectacle-corrected visual acuity, slit-lamp examination findings, intraocular pressure, fundus status, numerical density of endothelial cells, corneal thickness, and complications) were collected prospectively for all patients. RESULTS: After a median postoperative follow-up of 12 months (range, 8-18 months), a mean spherical equivalent of -0.50 +/- 0.87 diopter (range, +1 to -1.50 diopter) was achieved. The mean logarithm of the minimum angle of resolution visual acuity improved from 1 (preoperatively) to 0.1 (postoperatively) (P = 0.007, Wilcoxon test). Median endothelial cell losses of 15 +/- 8% (P = 0.008) and 14 +/- 16% (P = 0.011) were registered at follow-ups of 1 month and 12 months, respectively. Postoperative complications included chronic intraocular inflammation and superior corectopia. CONCLUSIONS: Our procedure appears to be a safe, accurate, stable, and efficacious option for the management of traumatic subluxated cataracts in adults. However, longer-term data are needed to evaluate the corneal endothelium.

Aged↗

Major endothelial loss from corneas in organ culture: importance of second endothelial count.

PURPOSE: The aim of this study was to show that major losses can still occur on corneas judged suitable for grafting at the first count. In addition, we studied the frequency of these losses on 1992 corneas over a period of 4 years to evaluate the risk incurred. METHODS: We evaluated the incidence of these major losses and the associated risk factors. An Ishigawa diagram was created with the Cornea Bank team and the ophthalmologists involved in organ retrieval. Endothelial losses caused by bacterial or fungicidal contamination were excluded from the study. For the 29 corneas that suffered major losses, we analyzed the donor files for donor age, clinical file, geographical origins of the corneas, the person who did the retrieval, the length of time the cornea was stored, the data resulting from examining the endothelium at the bank by optical microscope, and the method used for sterilizing the material used. Specific analyses in cases of major loss of endothelial content: anatomopathologic examination of the corneas and search for the herpes simplex virus (HSV; type 1 or 2) by polymerase chain reaction (PCR). We carried out a statistical analysis using a chi(2) test on the 1992 corneas studied to see if the presence of diabetes (type 1 or 2) in the donor led to reduction levels different from those of corneas originating from nondiabetic donors. RESULTS: The incidence was evaluated at between 0.4% and 3% of corneas sampled, and the associated risk factor was between 0.8% and 6% of grafted corneas. The occurrence of major losses was independent of donor age and was independent of the person who did the retrieval. The occurrence of major losses was independent of geographical origin. We tested our media for endotoxin before use and found levels from 0.22 to 3.9 UI/mL. We verified the absence of a chronological relationship between the batches of media used in the bank and the number of major losses observed, showing that the pyrogenicity limit was independent of cytotoxicity limits. Data analysis showed no difference in reduction levels between diabetic and nondiabetic donors (P < 0.05). Results on the detection of HSV-1 by PCR on the storage media were all negative, and these results agree with the anatomopathologic examinations that showed no signs of viral infection. CONCLUSION: Total endothelial losses amounted to 1.4%/yr. Without the double endothelial counts, we would have had 29 primary graft rejections over that period. During storage, this loss has not been linked to a specific cause, but risk factors such as traumatic death, herpes infections, and badly controlled endotoxin levels should be considered when taking preventative actions. For the moment, a second endothelial count before grafting should be carried out, because all these problem grafts conformed to grafting criteria after the first count. The possibility of carrying out this second count is one of the recognized advantages of storage in organ culture.

Adolescent↗

A novel in vitro model to study staphylococcal biofilm formation on intraocular lenses under hydrodynamic conditions.

PURPOSE: To develop a novel in vitro model to study the formation of Staphylococcus epidermidis biofilm on intraocular lenses (IOLs) from the primary-attachment phase to the biofilm-accumulation phase. The model was designed to replicate intraocular conditions especially by taking into account intraocular hydrodynamics. METHODS: The model consisted of Tygon tubing connected to a vial containing acrylic hydrophobic IOLs. Three septa, placed along the tubing, allowed, respectively, the artificial aqueous humor's arrival and its elimination and the bacterial suspension's inoculation. A first pump allowed the aqueous humor's movement along the circuit, whereas a second one regulated the flow at which the nutritive environment was regenerated. The whole circuit was placed in a 34 degrees C water bath. Every 2 to 4 hours, lenses were taken from this environment. Bound bacteria were removed by scraping of optical faces and counted. All data are presented as the mean, SD, and coefficient of variation (CV). Comparisons among experiments were performed by one-way analysis of variance (ANOVA). RESULTS: Calculated CVs were close to 30, showing that biofilm formation was homogeneous. Differences between experiments were nonsignificant for each removal time. The model provided the full kinetics of S. epidermidis biofilm growth on acrylic hydrophobic IOLs, with a stationary phase reached after 28 hours of incubation. CONCLUSIONS: Biofilm development is modulated by many variables, including environmental factors. The findings in the present study of bacterial colonization of IOLs under intraocular physiological conditions allow understanding and more accurate targeting of biomedical device-related infections such as endophthalmitis.

Acrylic Resins↗

Prognostic factors of liver metastases from uveal melanoma.

OBJECTIVES: This study was designed to assess survival and identify prognostic factors for liver metastases diagnosed by systematic screening in uveal melanoma patients. METHODS: Among 602 consecutive patients treated over 10 years for uveal melanoma and followed by systematic semi-annual hepatic screening (abdominal ultrasonography), 63 (10.5%) developed liver metastases; these patients form the basis of this study. Factors including patient demographics, characteristics of the uveal tumor, metastasis-free interval, severity of liver metastatic involvement, and treatments of metastases were studied retrospectively regarding their prognostic value, using univariate (Kaplan-Meier method) and multivariate (Cox model) analyses. RESULTS: Thirty-five patients (55.6% of the metastatic population) received systemic chemotherapy or best supportive care only; 14 patients (22.2% of the metastatic population) diagnosed with diffuse liver involvement had cytoreductive surgery and intra-arterial chemotherapy; 14 (22.2% of the metastatic population) had complete surgical removal of liver metastases followed by postoperative intra-arterial chemotherapy. No significant surgical complications were experienced. The median overall survival after diagnosis of liver metastases was 15 months. It reached 25 months for selected patients with complete resection (P=0.0002). In this cohort of 63 patients, ten or fewer preoperatively diagnosed metastases and primary uveal melanoma not involving the ciliary body were independently associated with better prognosis. CONCLUSIONS: This study suggests that selected patients with screened liver metastases from uveal melanoma may benefit from aggressive treatment, including surgery. The two independent favorable prognostic factors are fewer than ten metastases at screening and the absence of ciliary body involvement.

Adult↗

Ocular manifestations in congenital toxoplasmosis.

BACKGROUND: Retinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur. The aim of this study was to determine the nature of the latter in treated cases of the disease and to assess their impact on visual function. METHODS: Four hundred and thirty consecutive children with serologically confirmed congenital toxoplasmosis were included in this study. Data were prospectively collected using standardized ophthalmological assessment forms. The presence of retinochoroiditis and of associated pathologies was ascertained, and their impact on visual function was assessed. RESULTS: After a median follow-up of 12 years [range 0.6-26 years], 130 children manifested retinochoroiditis. We detected 22 foci of retinochoroiditis at birth and 264 additional ones during the follow-up period. Of these, 48 (17%) were active when first diagnosed. Twenty-five of the 130 children (19%) had other associated ocular pathologies. Of these, 21 (16%) had a strabismus, which was due to macular lesions in 86% of the cases; 7 (5.4%) presented with unilateral microphthalmia, and 4 (3%) with cataracts. Most of these events were detected after the onset of retinochoroiditis. None of the children presented with ocular involvement in the absence of chorioretinal lesions. Macular lesions occurred more frequently in children with associated pathologies (p<0.0001), and associated pathologies were likewise more common in individuals with macular lesions (p=0.0003). Visual impairment occurred in 31/130 cases, and in all but 3 of these eyes it was due not to an associated pathology but to macular retinochoroiditis. CONCLUSIONS: At the end of the follow-up period, ocular involvement existed in 30% of the treated children with congenital toxoplasmosis. Associated eye pathologies were manifested less frequently than anticipated. They may occur later in life and are an indirect marker of the severity of congenital toxoplasmosis, but they do not have a direct impact on visual acuity. The overall functional prognosis of congenital toxoplasmosis is better than would be expected on the basis of literature findings, with only 2 of the 130 children suffering bilateral visual impairment.

Adolescent↗

Treatment of liver metastases from uveal melanoma.

BACKGROUND: Uveal melanoma patients with liver metastases have a poor prognosis. The effect of screening and multimodality treatment (including surgery) should be evaluated. METHODS: A total of 602 patients treated for uveal melanoma during a 14-year period had abdominal ultrasonography screening every 6 months. Sixty-three developed liver metastases as the first extraocular metastatic site. When possible, liver surgery and intra-arterial catheter implantation were performed. The influence on survival of demographics, uveal tumor characteristics, liver metastasis presentation, and treatment was studied. RESULTS: The median time to liver metastasis was 29 months. Twenty-eight patients (44%) were operated on: 14 (22%) had R0 liver surgery, and 14 with diffuse liver involvement had R2 liver surgery (there were no significant surgical complications). Thirty-five patients with diffuse liver involvement received systemic chemotherapy or best supportive care only. The median overall survival was 15 months (range, 3-110 months): 25 months for the 14 patients with R0 surgery, 16 months for the 14 with R2 surgery, and 11 months for the 35 with chemotherapy or supportive care. By univariate analysis, age (< or =70 years), number of metastases (< or =10), and quality of operation (R0) were predictive of a better prognosis. CONCLUSIONS: In the case of liver metastases from uveal melanoma, aggressive treatment permitting tumor eradication seems to offer a chance of long-term survival to selected patients. Nevertheless, neither ultrasound screening nor quality of operation had an effect on the outcome of most patients (78%). Better screening tests and more effective multimodality treatments are required to improve survival in uveal melanoma patients with hepatic metastases.

Adult↗

Early CT-scan for chronic lacrimal duct symptoms - case report of a malignant melanoma of the lacrimal sac and review of the literature.

Malignant melanoma of the lacrimal sac is rare, and only 21 cases have been reported in the world literature. They have an insidious onset and may look like chronic dacryocystitis. In only 6 of these cases were there no recurrences. In most of the survivors, the diagnosis was made early which appears to be the most important prognostic factor. Hence a CT-scan in cases of persistent dacryocystitis is important. Melanoma of the lacrimal duct system is a good example of a condition requiring a multidisciplinary approach between ophthalmologist and maxillofacial surgeon. Any persistently symptomatic lacrimal duct system may need a maxillofacial consultation.

Chronic Disease↗

Prolonged survival after resection of liver metastases from uveal melanoma and intra-arterial chemotherapy.

BACKGROUND: To report the protracted 9-year survival of a patient after surgical management of multiple liver metastases from uveal melanoma. DESIGN: Interventional case report. METHODS: A 30-year-old patient, treated for choroidal melanoma by proton beam therapy, was semiannually followed by abdominal ultrasonography. Two years after initial treatment, a total body computed tomography scan suggested the diagnosis of isolated liver metastases. RESULTS: Multiple wedge resections and postoperative intra-arterial chemotherapy with fotemustine were performed. After 4 years, a metastatic nodule in the head of the pancreas was detected and surgically removed. Eighteen months later, metastases were progressively detected in other organs. The patient finally died of carcinomatous meningitis 9 years of first treatment of metastases. CONCLUSIONS: In the present case, the surgical control of liver metastases associated with intra-arterial chemotherapy prolonged the quality and length of life with progressive disease extension to other organs.

Adult↗

Intraocular microsporidiosis due to Encephalitozoon cuniculi in a patient with idiopathic CD4+ T-lymphocytopenia.

Encephalitozoon cuniculi was documented to cause disseminated microsporidial infection including an iris tumor and endophthalmitis in an adolescent with idiopathic CD4+ T-lymphocytopenia. The diagnosis was established by microscopic, serologic and molecular methods. E. cuniculi (rabbit strain) was identified from the iris tumor, as well as from urine, conjunctival, corneal, and nasal swabs. Treatment with oral albendazole led to rapid improvement. This case raises the possibility of disseminated microsporidial infection in the context of idiopathic CD4+ T-lymphocytopenia and possibly advanced human immunodeficiency virus (HIV) infection, and above all the possibility of intraocular infection with E. cuniculi in humans.

AIDS-Related Opportunistic Infections↗

In vitro influence of vancomycin on adhesion of a Staphylococcus epidermidis strain encoding intercellular adhesion locus ica to intraocular lenses.

PURPOSE: To assess anti-adhesion and/or bactericidal properties of vancomycin in vitro and to determine when these effects are detectable to estimate its relevance to perioperative antibiotic prophylaxis and analyze the efficacy of a newly designed vancomycin insert prototype for endophthalmitis prevention. SETTING: University research laboratory, Lyon, France. METHODS: Staphylococcus epidermidis clinical strain N890074 containing the intercellular adhesion locus ica was used as the infectious agent. Vancomycin was used at 20 microg/mL. A sterile biocompatible, biodegradable vancomycin insert, releasing 230 microg of antibiotics over 100 minutes, was designed especially for this study. To obtain bacterial killing curves, experiments were first performed in a 103 colony-forming units (CFU/mL) bacterial suspension containing no intraocular lenses (IOL). Then IOLs were incubated in the suspension, and bacterial adherence was determined using bacterial counting with and without antibiotic. RESULTS: Vancomycin (solution and insert) had an anti-adhesion effect after 1 hour and a relevant bactericidal effect after 6 hours of incubation. CONCLUSIONS: Vancomycin used with irrigating solutions does not remain in the anterior chamber long enough to develop bactericidal effect. Even if it initially reduces bacterial adhesion, used at a drug level dropping below the bacterial minimal inhibitory concentration, it could result in a secondary increase of the adhesion of slime-producing bacteria. A sufficiently high concentration was obtained in vitro by the new sustained-release system, thereby overcoming the theoretical drawback of a short half-life within the anterior chamber. Anti-adhesion and bactericidal action of vancomycin inserts remains to be confirmed in clinical studies.

Anti-Bacterial Agents↗

An ex-vivo, whole-globe porcine model of corneoepithelial wound healing tested using immunomodulatory drugs.

BACKGROUND: An efficient epithelial wound healing is essential for the preservation of vision. Hence, the effects of novel topical drugs on the ocular surface must be ascertained before clinical use. We have tested the utility of an ex vivo, whole-globe porcine screening model to serve as a partial substitute for resource- and time-consuming animal experiments. METHODS: Standardized corneoepithelial lesions, 5.0 mm in diameter and 40 microm in depth, were created with an Excimer laser in freshly enucleated porcine eyes. These were then exposed to control solutions (physiological saline (baseline), tissue-culture medium (positive control) and NH4 + (toxicity control)) and to three test agents (cyclosporin A, dexamethasone, and mitomycin C). The wound-healing response and toxic effects were monitored after 20-26 h by comparing lesion sizes. RESULTS: According to baseline data obtained using physiological saline, tissue-culture medium improved wound healing. The highest doses of NH4 + (1 M) and mitomycin C (1.0 mg/mL) elicited toxic effects (confidence interval according to Scheffé's post hoc test: -0.65 to -0.07 and -0.99 to -0.60, respectively). Under the same test conditions, cyclosporin A (0.1 to 10 mg/mL) and dexamethasone (0.1 to 10 mg/mL) had no influence on corneoepithelial wound healing. CONCLUSIONS: Drug screening with this ex vivo porcine model permits a reproducibly quantitative and time- and dose-dependent assessment of corneoepithelial wound healing. This model corresponds more closely to the clinical situation than cell culturing and may, therefore, be useful in evaluating novel pharmaceutical agents, thereby helping to cut down on the number of animal experiments performed prior to the instigation of clinical trials.

Animals↗

Reactivation of ocular toxoplasmosis during pregnancy.

We wished to assess whether ocular toxoplasmosis can be reactivated during pregnancy in immunocompetent females, and whether such reactivation is confined to the eye or whether the fetus is exposed to the risk of vertical transmission. For this purpose, we retrospectively examined 18 females with ocular toxoplasmosis during the course of 35 pregnancies. Of these 18 patients, seven developed recurrences during seven pregnancies. Due to the potential risk of functional damage to the mother and the possibility of vertical disease transmission to the fetus, we suggest following such cases carefully during pregnancy until the dimensions of the problem are more fully appreciated.

Female↗