Airbags and bilateral eye injury: five case reports and a review of the literature.

We report five cases of bilateral eye injuries from airbag deployment in motor vehicle crashes and review the world's literature on ocular injuries associated with airbags. The cases in the literature were identified by cross-referencing Medline searches from airbags and ocular injuries. Additional cases were identified after review of references from each article in the search. An additional 89 cases from the literature were identified and are included for discussion. Patients were treated individually in a noncontrolled, nonrandomized fashion according to the nature of each injury with regular follow-up examinations in clinic. Of the 94 cases studied, 24 (27%) were bilateral eye injuries, and 15 (16%) patients were wearing spectacles at the time of the accident. The most common injuries included corneal abrasions, eyelid trauma, and hyphemas. Outcomes ranged from complete resolution of symptoms and return of normal visual acuity to primary enucleation. This report describes the wide spectrum of eye injuries that may occur after airbag deployment. We suggest a management plan for the evaluation and treatment of the ocular complications of airbag-related trauma.

Atovaquone for the treatment of toxoplasma retinochoroiditis in immunocompetent patients.

OBJECTIVE: To report the results of a phase I trial to evaluate the safety and efficacy of atovaquone for the treatment of ocular toxoplasmosis in immunocompetent patients. DESIGN: Open label, nonrandomized, prospective, clinical trial. PARTICIPANTS: Seventeen immunocompetent patients between the ages of 18 and 75 years with clinical and serologic evidence of ocular toxoplasmosis participated. INTERVENTION: Treatment of ocular toxoplasmosis with atovaquone tablets (750 mg four times a day) for 3 months. Prednisone (40 mg) tablets were added on day 3 of treatment and tapered as inflammation resolved. MAIN OUTCOME MEASURES: Clinical response and patient tolerance to atovaquone therapy for ocular toxoplasmosis. RESULTS: Average follow-up was 10 months. Most patients experienced no adverse treatment effects. When present, side effects were usually mild and included rash, pruritus, headache, and nausea. With the exception of one patient, who discontinued treatment at 6 weeks secondary to persistent epigastric discomfort, all patients completed the 12 weeks of therapy. All patients had a favorable response to treatment that began within 1 to 3 weeks. Visual acuity was stabilized or improved in all patients. Median initial visual acuity was 20/200 and median final visual acuity was 20/25. In general, atovaquone was well tolerated. CONCLUSIONS: Atovaquone is better tolerated than conventional antitoxoplasmosis therapy and appears to be at least as effective. Atovaquone is a promising alternative for the treatment of ocular toxoplasmosis in immunocompetent patients.

Measurement of adenosine concentration in aqueous and vitreous.

PURPOSE: The release of adenosine by the ischemic retina may be an initial signal in the development of ischemic macular edema and neovascularization. The levels of adenosine have never been quantified in ocular fluids. In this study, a technique was developed for in vivo measurement of the concentration of adenosine in aqueous and vitreous. METHODS: Aqueous and vitreous samples were obtained from bovine eyes after death and from live porcine eyes with the subject under general anesthesia. Samples from live eyes were immediately incubated in the sampling syringe with pentoxifylline, erythro-9-(2-hydroxy-3-nonyl) adenine, and dipyridamole to prevent synthesis or degradation of adenosine during the collection procedure, filtered, and flash-frozen in liquid nitrogen. All samples were then filtered and purified on phenylboronate agarose columns and incubated with chloroacetaldehyde to convert the adenosine present in the sample to the fluorescent derivative 1,N6-ethenoadenosine. The 1,N6-ethenoadenosine was separated by high-pressure liquid chromatography and then measured by fluorometry. RESULTS: Levels of adenosine as low as 0.5 pmole could be detected with this procedure, compared with 20 pmoles by UV detection. By using this technique to measure adenosine levels in the eyes of normal weanling domestic pigs, it was determined that the adenosine concentration in the aqueous was 321.3 +/- 164.9 nM and in the vitreous was 210.8 +/- 41.5 nM. CONCLUSIONS: The conversion of adenine-containing compounds to fluorescent 1,N6-etheno derivatives offers analytical advantages of selectivity and sensitivity for the quantitative determination of these compounds, with the fluorometric detection providing substantially greater sensitivity than direct detection by UV absorption. The levels obtained in vivo from anesthetized but otherwise healthy pigs presumably reflected basal aqueous and vitreous adenosine levels under the described conditions. This method should be useful in investigating more directly the role of adenosine in models of retinal or ocular ischemia in vivo and in measuring adenosine levels in vitreous or aqueous samples from human patients.

Hypoxia precedes the development of experimental preretinal neovascularization.

BACKGROUND: Although the mechanism of preretinal neovascular growth in the cell-injected rabbit eye model is not known, it has been proposed that the initial vasodilation and eventual development of neovascularization may be attributable to inflammatory mediators. However, an alternative explanation involving hypoxia has not been considered. The purpose of this study was to measure preretinal oxygen tension prior to the development of preretinal neovascularization in the cell-injected rabbit eye. METHODS: In the rabbit, intravitreous injections of 250,000 homologous dermal fibroblasts were performed on one eye; the fellow (control) eye was injected with vehicle. Preretinal oxygen tension over the myelin wing was measured using 19F-NMR spectroscopy of a 30-microliters droplet of perfluorocarbon previously injected into the preretinal vitreous. RESULTS: Compared to control eyes, fibroblast-injected eyes showed a 1.7-fold decrease in preretinal oxygen tension from the first time studied (1 day after cell injection) through the development of visible neovascularization. Hypoxia occurred without coexisting ophthalmoscopic evidence of vascular occlusion or, on days 1 and 3 after cell injection, retinal detachment. CONCLUSION: This result demonstrates for the first time that preretinal hypoxia precedes the development of preretinal neovascularization in the fibroblast-injected rabbit eye.

Localization and quantitation of blood-retinal barrier breakdown in experimental proliferative vitreoretinopathy.

OBJECTIVE: To determine the contribution of the breakdown of the blood-retinal barrier (BRB) as measured with magnetic resonance imaging in the development of retinal detachment in an experimental model of proliferative vitreoretinopathy. METHODS: Contrast-enhanced magnetic resonance imaging was used to evaluate BRB breakdown in an intravitreal cell-injection model of proliferative vitreoretinopathy. Intravitreal injection of 2.5 x 10(5) homologous dermal fibroblasts produced specific disruption of the inner, or vascular, BRB. RESULTS: Breakdown of the BRB was greatest in the first 3 days after injection, confirming previous work using fluorescein-based methods. Injection of 1 mg of intravitreal triamcinolone acetonide at the time of cell injection significantly reduced both BRB breakdown and the incidence of eventual traction retinal detachment. Eyes that did develop detachment had significantly greater leakage prior to its development than those that did not, regardless of steroid treatment. CONCLUSIONS: Quantitation and definitive localization of BRB leakage with magnetic resonance imaging provides a better understanding of the relationship between BRB compromise and the development of retinal detachment in this frequently used model.

Accurate and precise measurement of blood-retinal barrier breakdown using dynamic Gd-DTPA MRI.

Dynamic T1-weighted magnetic resonance imaging (MRI) after the injection of Gd-DTPA is a promising method for investigating breakdown of the blood-retinal barrier (BRB). Previously, the authors demonstrated that in a T1-weighted image, the initial rate of change in the vitreous water MRI signal as gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enters the vitreous space strongly correlated with the extent of BRB breakdown. Here, a practical approach to measuring a more relevant physiologic parameter is presented: the permeability surface area product (PS). The theory is a development of earlier work used in investigating the breakdown of the blood-brain barrier. The accuracy and precision of this approach was investigated in rabbits pretreated with sodium iodate (30 mg/kg intravenously). The MRI-derived PS normalized to the area of leaky retina (5.65 +/- 0.25 x 10(-4) cm/min, mean +/- standard error of the mean; n = 6) was compared to a similarly normalized PS calculated using a classical physiologic method (4.12 +/- 0.73 x 10(-4) cm/min; n = 6). Good agreement between the two methods was found (P = 0.09). This result demonstrates that the MRI-derived PS is an accurate and precise measure of BRB breakdown under these conditions. The mathematical model of Gd-DTPA distribution in vivo also is validated. Based on these results, several potential sources of error are discussed, including the effect of back-flow of Gd-DTPA from the vitreous space to the plasma, the underlying vascular patency, and MRI slice selection.

In vivo imaging of breakdown of the inner and outer blood-retinal barriers.

Real-time contrast-enhanced magnetic resonance imaging (MRI) was used to distinguish between experimentally induced breakdown of the vascular (inner) and retinal pigment epithelial (RPE; outer) blood-retinal barrier (BRB) in vivo. Pigmented rabbits were treated with intravenous sodium iodate 30 mg/kg, (a specific RPE cell poison), intravitreal N-ethylcarboxamidoadenosine (NECA) 10(-3) mol/l (which specifically disrupts the vascular BRB), or retinal diode laser photocoagulation. Coronal T1-weighted proton images were acquired in a timed sequence after intravenous injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Images were analyzed to localize leakage of Gd-DTPA and determine the permeability surface area product normalized per unit area (PS). The pattern of enhancement observed in eyes treated with sodium iodate differed clearly from that in eyes treated with NECA. PS' values were significantly higher in eyes treated with sodium iodate than with NECA. Simultaneous leakage from the outer and inner BRB in eyes treated with dense retinal laser photocoagulation could be localized and quantitated independently.

Stimulation of cyclic adenosine monophosphate accumulation causes breakdown of the blood-retinal barrier.

Pigmented rabbits were given an intravitreous injection of 0.1 ml of various concentrations of test drug, and vitreous fluorophotometry was done 6 and 24 hr after injection. Dibutyryl cyclic adenosine monophosphate (AMP) and 8-bromo-cyclic AMP caused reversible intravitreous fluorescein leakage only at relatively high concentrations. Adrenergic agents that are effective stimulators of adenylate cyclase (epinephrine, isoproterenol, and norepinephrine) caused transient intravitreous fluorescein leakage (2.3-3.1-fold above baseline) that was significantly greater than that caused by phenylephrine (1.1-fold above baseline), an adrenergic agent that is a poor stimulator of adenylate cyclase. Prostaglandins E1 and E2, which are good stimulators of adenylate cyclase, caused striking disruption of the blood-ocular barriers, and prostaglandins that are not good stimulators of adenylate cyclase had little or no effect on these barriers. The magnitude of the prostaglandin E1 effect (9.3-fold above baseline) was similar to that of N-ethylcarboxamidoadenosine (NECA), the most potent adenosine agonist, and was greater than one would predict based on its effect on adenylate cyclase in vitro. Prostaglandin E1, like NECA, also caused retinal vasodilation and hemorrhages. These data suggest that stimulation of intracellular cyclic AMP accumulation may be a common feature of mediators that cause breakdown of the blood-retinal barrier, but there may be another as yet unexplained feature shared by PGE1 and NECA that makes them particularly effective and capable of causing retinal vasodilation and hemorrhages.

Current trends in suture fixation of posterior chamber intraocular lenses.

Corneal surgeons were surveyed with regard to their technique of suture fixation of posterior chamber intraocular lenses in the absence of posterior capsular support. Fifty-nine percent of the 260 respondents stated they perform the procedure almost exclusively during penetrating keratoplasty. Scleral fixation was marginally favored over iris fixation by these surgeons. Most intraoperative problems reported were related to the relative technical difficulty of the procedure, although transient hemorrhage from the ciliary body was also mentioned. Postoperative complications cited included mechanical problems involving the lens and iris, cystoid macular edema, glaucoma, and endophthalmitis.

Differentiation gradient of dopaminergic neurons in substantia nigra of rat.

The chemical differentiation featured by the appearance of tyrosine hydroxylase (TH) and the distribution pattern of the dopaminergic cells of rat substantia nigra (SN) were studied with combined immunocytochemical and electronmicroscopic techniques. Under the light microscope, the earliest TH-positive cells at embryonic day 13 are localized at the ventral part of rostral midbrain. Later appearing TH-positive cells join the earlier ones dorsally and caudally. As to the stain intensity and morphology of the labeled cells in the region of the SN, there exists a ventral to dorsal and lateral to medial spatiotemporal gradient, namely the cells in the ventral and lateral parts, compared with the dorsal and medial ones, have more intense staining, larger cell bodies with smaller nuclei and more and longer processes. The earliest nigrostriatal projection fibers stem from the most laterally located SN cells. Under electron microscope, rough endoplasmic reticula are always seen within the positively stained cells. With the progression of development, the cells show more intense staining and contain more rough endoplasmic reticula and other organelles. Together with the results reported on the neurogenesis and migration of the SN cells, the present study indicates that the chemical differentiation of SN cells, with a spatiotemporal gradient, starts after the completion of cell migration, a process paralleling to their morphological differentiation.

Intravitreous injection of adenosine or its agonists causes breakdown of the blood-retinal barrier.

Pigmented rabbits were anesthetized and given an intravitreous injection of 0.1 mL of a test substance or vehicle alone. Vitreous fluorophotometry was performed before injections and at various time points after injections. Compared with pretreatment scans, vehicle-injected eyes showed no change in intravitreous fluorescein sodium leakage at 6 and 24 hours after injection. Injection of adenosine (10(-2) mol/L) resulted in fluorescein leakage that was significantly greater than that which occurred in control eyes at 6 hours after injection, but returned to baseline at 24 hours. This effect was significantly attenuated by an adenosine receptor antagonist (BW-A1433U), suggesting that it was mediated by specific adenosine receptors. A nonselective adenosine receptor agonist, N-ethylcarboxamidoadenosine, and two relatively A1 selective receptor agonists, N6-cyclopentyladenosine and N6-phenylisopropyladenosine, also caused dose-dependent intravitreous fluorescein leakage. The relative order of potency was N-ethylcarboxamidoadenosine much greater than N6-phenylisopropyladenosine, which was greater than N6-cyclopentyladenosine, implicating A2 adenosine receptors. Intravitreous injection of dipyridamole, an adenosine uptake inhibitor, caused enhanced fluorescein leakage, presumably from extracellular accumulation of endogenous adenosine. The results of this study suggest that adenosine may be a mediator of blood-retinal barrier breakdown.

Adenosine and its agonists cause retinal vasodilation and hemorrhages. Implications for ischemic retinopathies.

Animals were given a 0.1-mL intravitreous injection of various agents and followed up with frequent ophthalmoscopic examinations. Fundus photographs were performed before injection and at six and 24 hours after injection. Vascular caliber was assessed by a previously described technique of performing measurements on fundus photographs taken and projected in a standardized fashion. No significant vascular dilation was identified for vehicle alone, carbachol, histamine, isoproterenol hydrochloride, or bradykinin. Mild dilation within one hour, but not persisting for 24 hours, was noted for dibutyryl cyclic adenosine monophosphate. Prominent dilation within one hour, becoming maximal by five hours but not persisting for 24 hours, was noted for adenosine, dipyridamole, and sodium nitroprusside. The adenosine-induced vasodilation was effectively blocked by an adenosine receptor antagonist, BW-A1433U. N-ethylcarboxamidoadenosine (NECA), a nonspecific adenosine selective agonist, was a much more potent vasodilator than two relatively selective A1 adenosine agonists, N6-cyclopentyladenosine and N6-phenylisopropyladenosine, suggesting that A2 receptors are involved. The vascular dilation caused by adenosine, dipyridamole, and particularly NECA, but not nitroprusside or dibutyryl cyclic adenosine monophosphate, was accompanied by retinal hemorrhages, producing a picture reminiscent of some features of ischemic retinopathies. This study suggests that adenosine may be an important mediator of vasodilation, and therefore blood flow, in the retina.

The role of breakdown of the blood-retinal barrier in cell-injection models of proliferative vitreoretinopathy.

Rabbits were given an intravitreous injection of 5.0 x 10(5) rabbit retinal pigment epithelial (RPE) cells, human RPE cells, or human dermal fibroblasts in one eye and an injection of vehicle alone in the other eye. Some rabbits were treated with retinal cryopexy or intravenous sodium iodate on the day before injection. Vitreous fluorophotometry (VFP) and fundus examinations were performed before and at various times after cell injections. Retinal detachments were graded by premortem ophthalmoscopic examinations and postmortem gross pathologic examinations. Eyes injected with cells had higher VFP readings than eyes injected with vehicle at all time points. Eyes injected with fibroblasts or rabbit RPE had significantly higher mean VFP values before the onset of retinal detachment than those injected with human RPE cells. Within each group, high levels of fluorescein leakage in the first week correlated well with severity of subsequent traction retinal detachment and the fibroblast and rabbit RPE groups had more severe detachments than the human RPE group. Treatment with cryopexy or sodium iodate resulted in higher VFP readings, a higher frequency of retinal detachments, and detachments that occurred earlier and that were more severe. These data demonstrate that intravitreous cells cause blood-retinal barrier breakdown in rabbits and that the amount and duration of this breakdown are important variables in retinal detachment formation.