Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Human corneal stromal tissue concentration after consecutive doses of topically applied 3.3% vancomycin.

AIMS: To evaluate vancomycin penetration into human corneal stromal tissue in patients treated with topical vancomycin eyedrops before penetrating keratoplasty (PKP). METHODS: Twenty four patients who underwent PKP, seven patients with keratoconus (group 1) and 17 patients with corneal scar or corneal decompensation (group 2). All patients received topical application of vancomycin eyedrops (concentration: 33 mg/ml) 10, 3, 2, 1 hour, and 15 minutes before the operation. Corneal cumulative vancomycin levels were assessed by bioassay. RESULTS: Mean vancomycin corneal stromal tissue concentration was 46.7 (SE 4.11) microg/g tissue. This value was four to 20-fold in excess of the MIC90 of vancomycin in Staphylococcus aureus (2-10 microg/ml). CONCLUSIONS: Vancomycin reached high corneal tissue concentrations that significantly exceeded the MIC90 (2-10 microg/ml) for most key Gram positive corneal pathogens. The ratio of vancomycin stromal concentration to protein concentration was statistically higher in group 2 (non-keratoconus).

Unrecordable pulsatile ocular blood flow may signify severe stenosis of the ipsilateral internal carotid artery.

AIM: To examine the relation between stenosis of the internal carotid artery (ICA) and pulsatile ocular blood flow (POBF). METHODS: In 57 eyes of 30 patients who were referred for Doppler ultrasound examination of the ICA we measured POBF and analysed the correlation with degree of ipsilateral ICA stenosis. RESULTS: There was a significant negative correlation between POBF and ipsilateral ICA stenosis (Pearson correlation coefficient, r=-0.516, p<0.0001). In 14 eyes POBF could not be measured by the OBF tonometer, and in 11 of these cases (79%) severe stenosis (>75%) of the ipsilateral ICA was present. When these eyes were excluded from analysis, there was no correlation between POBF and ICA stenosis (r=-0.02, p=0.91). Among these 43 eyes in which POBF could be measured it ranged 667-2095 microl/min with a mean of 970.72 microl/min. CONCLUSION: Low or unrecordable POBF may signify severe stenosis of the internal carotid artery. POBF is not a direct reflection of ipsilateral ICA blood flow.

Ocular hypotensive effects of cholinergic and adrenergic drugs may be influenced by prostaglandins E2 in the human and rabbit eye.

PURPOSE: Increased PGE2 production by the iris and ciliary body regulate intraocular pressure (IOP) in vivo. Various cholinergic and adrenergic compounds are traditionally used as antiglaucoma drugs, and their effect on IOP reduction is antagonised by cyclooxygenase inhibitors, indicating a role for eicosanoids in their hypotensive activity. One of the most potent antiglaucoma drugs, PG2 alpha (Latanoprost), reduces IOP by increasing uveoscleral outflow and also increases PGE2 production by the iris and ciliary body in vivo. We investigated whether cholinergic and adrenergic antiglaucoma drugs induce the production of prostaglandin E2 (PGE2) in vitro by: 1) the iris-ciliary body (ICB) of rabbits and, 2) irises of glaucoma patients. METHODS: Pilocarpine 2%, epinephrine 1% and echothiophate iodide 0.125% were applied topically to both eyes of Albino rabbits. Control groups were treated with the corresponding vehicles, or untreated completely. Human iris specimens were obtained from nine untreated cataract eyes, and five eyes under antiglaucoma medication undergoing surgery. PGE2 were determined by a radioimmunoassay. RESULTS: PGE2 production by the ICB of treated rabbits in vitro was twice that of vehicle-treated or untreated rabbit eyes (p<0.001, for either group). In vitro PGE2 production by treated glaucoma patients' irises was three times higher (p<0.001) than in cataract control patients. CONCLUSIONS: The study found an increase in in vitro production of PGE2 by the irises of eyes treated with cholinergic and adrenergic antiglaucoma medications. This suggests a role for endogenous PG production in the hypotensive effect of both classes of drug.

Corneal surface changes after pars plana vitrectomy and scleral buckling surgery.

PURPOSE: To evaluate the changes in corneal shape after pars plana vitrectomy, encircling buckling surgery, and a combination of the 2 procedures. SETTING: Assaf Harofeh Medical Center, Zrifin, and Goldshlager Eye Institute, Tel Hashomer, Israel. METHODS: In a prospective clinical study, 61 eyes of 61 patients were assigned to 1 of 3 groups based on the type of procedure: pars plana vitrectomy, encircling buckle and pars plana vitrectomy, or encircling buckle. The eyes had corneal keratometry (TMS-1), visual acuity measurement, and videokeratography (TMS-1) preoperatively and 2 days, 1 week, and 1 and 3 months postoperatively. The topographic parameters statistically analyzed were the corneal surface cylinder, simulated keratometry, surface regularity index, surface asymmetry index, standard deviation of corneal power, average corneal power, and irregular astigmatism index. RESULTS: The measurements of all topographic indices were statistically significantly different from baseline measures 2 and 7 days postoperatively in all 3 groups. However, at 1 and 3 months, there was no significant difference from preoperatively in any index. Postoperative best corrected visual acuity was statistically significantly different from preoperatively. CONCLUSIONS: All corneal surface indices were significantly altered after all 3 types of surgery. Corneal surface measurements returned to preoperative values by 1 month postoperatively and remained stable until the final follow-up at 3 months.

The reculture technique: individualizing the treatment of Acanthamoeba keratitis.

PURPOSE: To assess the efficacy of three drugs in different concentrations against different strains of Acanthamoeba using the reculture technique. METHODS: Cysts and trophozoites were immersed in five separate solutions. The solutions administered included 0.1% and 0.02% polyhexamethylene biguanide (PHMB), 0.1% and 0.02% chlorhexidine, and propamidine isethionate (Brolene). Readings took place after 1, 5, and 24 hours. The cysts and trophozoites were then recultured for an additional period of 48 hours. An effective drug was defined as a medication that inhibited any growth of trophozoites using the reculture technique. RESULTS: Chlorhexidine at concentrations of 0.1% and 0.02% was the only effective drug against all five strains of Acanthamoeba examined, and no trophozoites were detected on plates immersed with this agent. Only 0.1% chlorhexidine was effective in destroying all cysts in the five strains examined. CONCLUSION: We found that 0.02% chlorhexidine was efficient in irradicating all trophozoites and 0.1% chlorhexidine was effective in eradicating all cysts in the samples we examined. Therefore, it may be possible that 0.02% chlorhexidine is a good initial treatment in amoebic keratitis. Sensitivity testing, then, may be performed using the reculture technique and specification of therapy can be made accordingly.

The incidence of hepatitis C virus positive serological test results among cornea donors.

Purpose. We have noticed that the incidence of positive serological tests of hepatitis C virus (HCV) among cornea donors in our eye bank is higher than expected. The purpose of this study was to determine the incidence of these positive findings and identify the contributory risk factors.Methods. All corneas procured between June 1993 and June 1997 were included in this retrospective study. In all cases a routine work-up, including serological testing of donors' sera and evaluation of the procured corneas, was performed prior to corneal transplantation. Donors found to be positive for HCV antibodies were compared to our general population of corneal donors, with respect to the demographic, serological and ophthalmological data obtained during the transplantation work-up.Results. All 851 corneas procured from 438 donors were included. Antibodies to HCV were found in 29 donors (6.6%). Following positive test results, 57 corneas (6.7%) were discarded. The time from donors' death to cornea procurement was significantly longer among HCV-positive patients than in the general donor population (12.3 vs. 9.3 h, p<0.0003). No other differences were detected between the two groups.Conclusion. Delay in harvesting of donated corneas may give rise to false positive HCV-antibodies test results, which may be partially responsible for the high rate of positive findings among cornea donors, with consequent tissue wastage.

Persistent chlorpromazine deposits in donor corneal tissue after corneal transplantation.

PURPOSE: To present unusual cases with corneal graft deposits and discuss eye bank criteria concerning donors treated with phenothiazines. METHODS: We examined two patients with unusual corneal graft deposits after uneventful corneal transplantation. Donors' files and eye bank procedures were reviewed. RESULTS: Fine corneal endothelial punctate deposits were detected in both corneal grafts and did not resolve in the following 18 months. CONCLUSION: To our knowledge, this is the first case report documenting transplantation of corneas with chlorpromazine deposits. Delicate corneal findings can be missed before transplantation.

Drug induced myopia associated with treatment for gynecological problems.

We present three cases of women who developed acute transient myopia caused by drugs for gynecological problems. One patient was treated with disothiazide for premenstrual edema. The second had acute cystitis and was treated by sulphonamide and the third developed myopia coincident with metronidazole treatment for trichomonas vaginalis. We followed these patients by A scan ultrasonographic ocular measurements, documenting reduction of the anterior chamber depth combined with lens thickening. The ocular and myopic changes cleared up completely on discontinuation of the causative agent. The possible mechanism is thought to be an allergic reaction to the drug.

Sjogren's syndrome in Israel: primary versus secondary disease.

Sixty Israeli patients, 30 with primary Sjögren's syndrome (SS) and 30 with rheumatoid arthritis (RA) and secondary SS, were evaluated. The Schirmer-1 test and a positive labial salivary gland biopsy were found to be the most helpful tools in assessing the diagnosis of SS. Extraglandular features such as Raynaud's phenomenon, lymphadenopathy and CNS involvement as well as parotid gland enlargement (p < 0.05) were more common in primary SS. Antinuclear antibodies, especially anti-Ro (SSA) and anti-La (SSB) were also more common in primary SS (p < 0.05). Our results are in accord with those of many European centers, despite the different genetic background.

Dislocation of a scleral-fixated, posterior chamber intraocular lens after fixation suture removal.

A 58-year-old man's posterior chamber intraocular lens dislocated after a transscleral fixation suture was removed during a routine eye examination. The lens had to be repositioned. A scleral flap over the fixation sutures and a better understanding by general ophthalmologists of transscleral fixation suturing would have prevented this complication.

Proximity-sensor dimmer device as an aid in the reduction of operating microscope-induced retinal phototoxicity.

The length of exposure to the light source of the operating microscope is a major factor determining retinal phototoxicity. In our experience, for about 20% of the time during cataract surgery, the surgeon is not looking through the oculars. To take advantage of these times, we designed a device, a proximity switch consisting of an infrared sensor mounted between the oculars in the operating microscope. When the surgeon's forehead approaches the microscope to look through the oculars, the sensor increases the illumination; when the surgeon moves away, it is automatically reduced. The resulting decreased overall exposure to light may reduce retinal phototoxicity.

Using an anterior chamber maintainer to control intraocular pressure during phacoemulsification.

We describe a phacoemulsification technique that uses an anterior chamber maintainer (ACM) to control intraocular pressure. Continuous irrigation through the ACM maintains pressurized intraocular conditions throughout surgery and when the automated system is not activated. Intraocular pressure is stabilized at predetermined levels with minor fluctuations. Viscoelastics can be used in conjunction with the ACM.