Results of macular pucker surgery: 1- and 5-year follow-up

Background  Although macular pucker removal in patients with metamorphopsia due to a macular pucker is a traditional elective vitreoretinal indication, we found that patients were not uniformly satisfied after surgery. We wished to study outcome in vision and metamorphopsia in patients undergoing macular pucker surgery, to assess changes between 1- and 5-year follow-up, as well as patient satisfaction at 5 years. Methods  We assessed 107 consecutive patients undergoing macular pucker surgery and subsequent cataract surgery when not already pseudophakic. Early Treatment of Diabetes Study (EDTRS) vision and Sine Amsler Chart metamorphopsia grading were assessed before surgery and 1 year postop in 107 patients. In 57 patients we obtained a 5-year vision, metamorphopsia grading and a response to a questionnaire. Results  After 1 year, mean vision had improved 2 ETDRS lines and metamorphopsia had decreased in 83% of the patients. The 57 patients returning for the 5-year follow-up and questionnaire had a statistically significantly greater improvement in vision at 1 year than those who did not return. In these 57 patients, a further mean increase of 1 ETDRS line had occurred, as well as a further decrease in metamorphopsia in one third of the patients. Forty of 57 patients (70%) indicated that they would elect to have surgery again. Reasons for not returning after 5 years, however, were probably related to dissatisfaction in at least one third of patients. Conclusions  Although macular pucker surgery resulted in an increase in vision and a decrease of metamorphopsia in 83% of patients after 1 year, we assume, based on the biased patient sample we questioned after 5 years, that subjective assessment would be positive in only a small majority of the patients.     

Corneal flap displacement and drift in LASIK: comparison of Hansatome and Automated Corneal Shaper microkeratomes

PURPOSE: To describe and compare the displacement of corneal flaps created during laser in situ keratomileusis (LASIK) procedures performed with two different microkeratomes and analyze parameters (for example, pupil-to-hinge distance, drift during suction) that might affect the flap displacement or be influenced by flap displacement. DESIGN: This work was based on a cross-sectional study design. METHODS: Images copied from video recordings of 206 consecutive LASIK surgeries were analyzed to determine the distance from pupil center to corneal flap hinge (pupil-to-hinge distance), the hinge size, the distance from the center of the pupil to the margins of the flap, and the positions of the suction ring before and after vacuum in corneal flaps created by the Hansatome and the Automated Corneal Shaper (ACS) microkeratomes. Accurate measurements of all these variables could be obtained in 121 eyes (Hansatome: n = 66, right eye (OD) = 27 eyes, left eye (OS) = 39 eyes; ACS: n = 55, OD = 25 eyes, OS = 30 eyes), which were included in the analysis. Formulas were derived to calculate from the measurements the magnitude and direction of the drift of the suction ring during vacuum and the final displacement of the corneal flap. RESULTS: The mean +/- standard deviation (SD) drift of eyes during suction with the Hansatome was 0.27 +/- 0.02 mm and with the ACS was 0.12 +/- 0.02 mm (P <.001). The Hansatome induced, on average, more biased (temporal vs random) drift than did the ACS. The mean final displacement of the center of the flap from the center of the pupil was of equal magnitude for the two instruments (0.37 +/- 0.02 mm and 0.36 +/- 0.02 mm with the Hansatome and ACS, respectively). CONCLUSION: The drift induced by the Hansatome contributes to the horizontal component of the final decentration of the corneal flaps. This tendency for drift and the resultant decrease in pupil-to-hinge distance should be considered to minimize flap displacements during LASIK.     

Human corneal epithelial cell viability and morphology after dilute alcohol exposure

PURPOSE: To determine the effect of dilute alcohol on human corneal epithelial cellular morphology and viability. Dilute alcohol is used for epithelial removal during photorefractive keratectomy (PRK) and laser subepithelial keratomileusis (LASEK). METHODS: Corneal epithelial sheets harvested from human eyes after alcohol application during PRK were examined by light and electron microscopy (specimens I-IV). In addition, tissue cultures of human epithelial sheets were monitored for epithelial migration and attachment (specimens V-VII). To determine the effect of dilute alcohol on epithelial cell viability, simian virus (SV)40-immortalized human corneal epithelial cells were exposed to dilute alcohol in distilled water (EtOH-H2O) or to keratinocyte serum-free medium (EtOH-KSFM) for incubation periods of 20 to 45 seconds and concentrations of 10% to 70%. Cell membrane permeability and intracellular esterase activity were analyzed by calcein-acetoxymethyl ester (AM)/ethidium homodimer assay. TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect apoptotic cells at 0, 8,12, 24, and 72 hours. RESULTS: Electron microscopy showed varying degrees of basement membrane alterations after alcohol application, including disruptions, discontinuities, irregularities, and duplication (specimens I-IV). Cellular destruction and vacuolization of basal epithelial cells associated with absent basement membrane were also observed (specimen III). One of three cultured epithelial sheets showed attachment and outgrowth in the tissue culture until day 15 (specimen V). Twenty-second exposure of cultured immortalized human cells to various concentrations of EtOH-H2O showed significant reduction of viable cells when EtOH-H2O concentration exceeded 25% (P = 0.005). Increasing the duration of application of 20% EtOH-H2O beyond 30 seconds resulted in a significant reduction in viable cells (69.69% +/- 16.34% at 30 seconds compared with 2.14% +/- 2.29%, 10.45% +/- 7.11%, and 11.09% +/- 15.73% at 35, 40, and 45 seconds, respectively; P = 0.01). TUNEL assay of cultured human corneal epithelial cells exposed to 20% EtOH-H(2)O for 20 and 40 seconds showed maximal labeling at 24 hours (58.05% +/- 33.10%) and 8 hours (94.12% +/- 1.21%), respectively. Exposure to 20% EtOH-KSFM for 20 and 40 seconds resulted in substantially lower TUNEL positivity (3.51% +/- 0.20% at 24 hours and 7.11% +/- 0.49% at 8 hours). CONCLUSIONS: The viability and electron microscopic findings in the basement membrane zone showed significant variation after treatment of the epithelium in vivo with dilute alcohol. The application of dilute alcohol on the monolayer of cultured corneal epithelial cells resulted in increasing cell death in a dose- and time-dependent manner.     

Relative picrotoxin insensitivity distinguishes ionotropic GABA receptor-mediated IPSCs in hippocampal interneurons

Inhibitory GABAergic signalling in the hippocampus plays an important role in synchronizing principal cells and regulating the excitability of this seizure-prone structure. Distinct mechanisms modulate release from GABAergic terminals in the hippocampus, depending on whether the postsynaptic partner is an interneuron or a principal cell. Here, we report that postsynaptic ionotropic GABA receptors in principal cells and interneurons also show a striking pharmacological difference. The broad-spectrum antagonist picrotoxin (PTX) was less potent at blocking IPSCs evoked in stratum radiatum interneurons than in pyramidal neurons in the CA1 region. GABA-evoked currents in membrane patches from interneurons showed a smaller mean unitary conductance than in patches from pyramidal neurons. Because retinal GABA(C) receptors show decreased picrotoxin sensitivity and conductance, we examined the effect of the GABA(C) receptor agonist cis-aminocrotonic acid (CACA). Although this agent evoked picrotoxin-resistant currents in interneurons, these were enhanced by the GABA(A) allosteric modulator pentobarbital. Moreover, both picrotoxin-resistant IPSCs and CACA-evoked currents were blocked by the GABA(A) receptor-selective antagonist bicuculline. The presence of relatively picrotoxin-resistant GABA(A) receptors in interneurons provides a potential target for agents to modulate the activity of sub-populations of hippocampal neurons.     

A 55-year-old mechanically ventilated male requiring aeromedical evacuation

Objective: To present a case that illustrates the problems unique to transporting a mechanically ventilated patient by air. A 55-year-old mechanically ventilated male with Guillain-Barre Syndrome, a condition with respiratory effects often similar to those of traumatic brain injury, required air transport from Walter Reed Army Medical Center in Washington, DC, to a hospital in Nevada. A medical team, including one physician, one nurse, and one respiratory therapist, accompanied the patient. This team was not trained in air travel and its unique risks. To complete the mission they had to rapidly familiarize themselves with the specific risks of air travel and the precautions that should be taken. This case is presented to illustrate these risks and what can be done during flight to minimize them.     

Synthesis,beta-adrenoceptor pharmacology and toxicology of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride,a short acting beta(1)-specific antagonist

The synthesis of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride (D140S.HCl 6), a novel short acting beta(1)-specific adrenoceptor antagonist, has been described. The antagonist potency for D140S.HCl 6 has been compared with esmolol, another short acting agent, and other well known beta-adrenoceptor antagonists in isolated rat tissue preparations. The pharmacokinetics of D140S.HCl 6 in 7 day continuous intravenous infusions and 4 weeks intravenous bolus injection studies in conscious rats and dogs have been examined in toxicology studies. The effect on the isoprenaline-induced heart rate increase and the pharmacodynamic half-life of D140S.HCl 6 has been compared with esmolol in a conscious rat model. In addition, the results of a range of toxicological studies are presented. The results indicate that D140S.HCl 6 is a highly specific beta(1)-adrenoceptor antagonist (pA(2) = 8.15+/-0.22, beta(1)/beta(2) selectivity > 4400). The in vitro studies suggest D140S.HCl is ca. ten times more potent and 60 times more beta(1)-specific than racemic esmolol. Pharmacokinetic non-linearity was seen when given as a 7 day intravenous infusion at toxicological doses above 10 mg kg(-1) h(-1) in the rat and 2.5 mg kg(-1) h(-1) in the dog. Both D140S.HCl 6 and esmolol have very short durations of action after intravenous infusion in the rat (pharmacodynamic half-life is < 15 min for D140S.HCl and 10 min for esmolol). The toxicological tests indicate that D140S.HCl 6 shows no unexpected toxicity and none of the tissue irritancy problems reported for esmolol formulations.