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Biomedical subjects

Justus G Garweg

Publications and source records attributed to Justus G Garweg.

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↗

The antibody response in experimental ocular toxoplasmosis.

BACKGROUND: The dynamics of the humoral immune response in ocular toxoplasmosis (OT) are poorly understood. We therefore investigated this process in a rabbit model of the disease. MATERIALS AND METHODS: Of 24 infection-naive adult rabbits, 12 were left untreated and 12 were systematically infected with 5,000 tachyzoites of the non-cystforming BK strain of Toxoplasma gondii. Three months later, all rabbits were inoculated transvitreally with 5,000 tachyzoites of Toxoplasma gondii. Paired samples of aqueous humor and serum were analyzed temporally for their total and specific IgG contents. RESULTS: In infection-naïve rabbits with primary OT, specific IgG reached detectable levels in the inoculated eyes between 5 and 15 days after inoculation. In infection-immunized rabbits with secondary OT, a significant increase in specific IgG was regularly detected after 5 days. The antibody ratio C was diagnostic (> or =3) from day 15 onward in primary OT and from day 21 onward in secondary OT. In the uninfected partner eyes, the antibody ratio C was found sporadically diagnostic from day 15 onward in primary OT, but at no time in secondary OT. Specific IgG persisted both locally and in the serum until the end of the monitoring period (100 days). CONCLUSION: Our findings relating to the rabbit model of OT reveal three features of clinical relevance: a diagnostic window precedes the establishment of a humoral immune response; specific antibodies persist long after the cessation of disease activity; and in primary OT, the antibody ratio C may also increase in the uninfected partner eye.

Animals↗

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↗

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↗

Effects of daunorubicin, mitomycin C, azathioprine and cyclosporin A on human retinal pigmented epithelial, corneal endothelial and conjunctival cell lines.

BACKGROUND: We wished to investigate the toxicity of four immunosuppressant and antimetabolic drugs, which are known to influence postoperative wound healing, on three different human ocular cell lines. METHODS: Acute toxicity to cyclosporin A, azathioprine, mitomicyn C and daunorubicin was assessed in Chang cells by monitoring their uptake of propidium iodide during a 3-h period. Chronic toxicity was assessed by monitoring the proliferation and viability of subconfluent cultures of Chang cells, human corneal endothelial cells (HCECs) and retinal pigmented epithelial (RPE) cells after continuous exposure to the drugs for 7 days. RESULTS: Acute toxicity testing revealed no obvious effects. However, the chronic toxicity tests disclosed a narrow concentration range over which cell proliferation decreased dramatically but calcein metabolism was sustained. Although the three lines reacted similarly to each agent, HCECs were the most vulnerable to daunorubicin and mitomycin. At a daunorubicin concentration of 0.05 microg/ml, a 75% decrease in calcein metabolism (P < 0.001) and a > or = 95% cell loss (P < 0.001) were observed. At a mitomycin concentration of 0.01 mug/ml, cell density decreased by 61% (P < 0.001) without a change in calcein metabolism, but at 0.1 microg/ml, the latter parameter decreased to 12% (P = 0.00014). At this concentration the proliferation of Chang and RPE cells decreased by more than 50%, whilst calcein metabolism was largely sustained. Cyclosporin inhibited cell proliferation moderately at lower concentrations (< 5 microg/ml; P=0.05) and substantially at higher ones, with a corresponding decline in calcein metabolism. Azathioprine induced a profound decrease in both parameters at concentrations above 5 microg/ml. CONCLUSION: Daunorubicin, cyclosporin and azathioprine could be used to inhibit excessive intraocular scarring after glaucoma and vitreoretinal surgery without overly reducing cell viability. The attributes of immunosuppressants lie in their combined antiproliferative and immunomodulatory effects.

Antimetabolites↗

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↗

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↗

Specific antibody levels in the aqueous humor and serum of two distinct populations of patients with ocular toxoplasmosis.

The population of Erechim, Southern Brazil, is characterized by a high incidence of ocular toxoplasmosis, which is presumed to be of acquired origin. We wished to compare the local specific humoral immune response of individuals from this region with that of Swiss patients suffering from the same disease. Paired samples of aqueous humor and serum were withdrawn from 27 Brazilian and 50 Swiss patients presenting consecutively with active ocular toxoplasmosis. The total and specific levels of IgG in each of these were determined. The populations did not differ with respect either to age or sex. The serum levels of total IgG in Brazilian (10.8 g/l) and Swiss patients (11.1 g/l) were similar (p = 0.499), but the aqueous humor ones were higher in the former group (95 vs. 20 mg/l; p = 0.0001). The systemic and local levels of specific IgG were likewise higher in Brazilian patients [206 i.u. vs. 72 i.u. (p = 0.001) and 14 i.u. vs. 4 i.u. (p = 0.005), respectively] and the number of individuals without detectable levels of local specific IgG was correspondingly lower (11% vs. 54%; p = 0.0005). The Goldmann-Witmer coefficient (an index of local specific antibody production) did not differ between Brazilian and Swiss patients (2.1 vs. 0.08, respectively; p = 0.107). Our findings are indicative of a more pronounced uveovascular barrier breakdown in Brazilians than in Swiss patients with active ocular toxoplasmosis. That the systemic and local specific immune response is weaker in Swiss than in Brazilian patients has not been hitherto documented. This finding may reflect differences in the immunological handling of the infection.

Adult↗

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↗

Atypical Vogt-Koyanagi-Harada disease or new uveomeningitic syndrome?

PURPOSE: To report on a patient affected by bilateral intermediate uveitis (IU) as the initial sign of an uveomeningitic syndrome. METHODS: Thorough history, physical examination and ancillary laboratory and radiological testing were performed in this observational case study. RESULTS: A 23-year-old Caucasian man developed bilateral IU, primarily diagnosed as "idiopathic" since a detailed etiologic work-up was not indicative of underlying disease. Seven months later, he presented with poliosis and vitiligo. Lumbar puncture revealed cerebrospinal fluid pleocytosis. Optical coherence tomography showed bilateral subclinical macular edema (ME). The visual acuity was still 20/20 in both eyes. Clinical, laboratory and radiological results did not fit into any known syndrome. CONCLUSIONS: According to all the tests performed, the disease in our patient is a uveomeningitic disease with IU and ME which could be interpreted as an atypical form of Vogt-Koyanagi-Harada disease or a new uveomeningitic syndrome because there is no evidence for any other known disease.

Adult↗

Evolution of HIV-1-related conjunctival molluscum contagiosum under HAART: report of a bilaterally manifesting case and literature review.

PURPOSE: To present a rare case of bilateral conjunctival molluscum contagiosum (MC) in an HIV-positive individual who had unilateral lesion excision before induction of highly active antiretroviral therapy (HAART), and to discuss the pathophysiological consequences of immune restoration. METHODS CASE REPORT: A 40-year-old male Caucasian presented with atypical, bilateral lesions of the limbal conjunctiva due to MC. Before the induction of HAART, nodules in the left eye were excised whilst the single lesion in the right eye was left untouched. RESULTS: The clinical diagnosis of conjunctival MC was confirmed histopathologically. Six months after the induction of HAART, the untouched lesion (right eye) had regressed and there was pronounced local injection of the conjunctiva. MC lesions did not recur after excision (left eye), and signs of inflammation were absent. CONCLUSION: Conjunctival MC is rare and associated with immune deficiency. To the best of our knowledge, the presented case is the first reported instance of bilateral, multi-lesional MC of the conjunctiva in an HIV-positive patient undergoing HAART. Attention must be paid to the possible complications associated with the restoration of immunocompetence.

Adult↗

Bilateral rhegmatogenous retinal detachment after external-beam radiotherapy: just a coincidence?

PURPOSE: To report an unusual case of almost simultaneous bilateral rhegmatogenous retinal detachment in the context of external-beam radiotherapy for a tumor at a non-ocular target site and in the absence of pre-existing ocular pathology. METHODS: Observational case report with review of corresponding literature. RESULTS: A 63-year-old man was referred for bilateral retinal detachment which was associated with many horseshoe tears and proliferative vitreoretinopathy. He had undergone surgery for a carcinoma of the left maxillary sinus 4 months prior to the presentation and had then received external-beam radiotherapy for 3 months. There was no familial history of retinal detachment and/or eye trauma in this hyperopic patient with clear native lenses. No chorioretinal pathology was apparent that could have predisposed the retinas to tearing. CONCLUSIONS: Simultaneous bilateral retinal detachment is exceptional, especially in a patient with no risk factors. The effect of radiotherapy on the vitreoretinal interface is discussed in the light of existing data and may have been responsible for our patient's retinal detachment.

Functional Laterality↗