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Biomedical subjects

Terrence P O'Brien

Publications and source records attributed to Terrence P O'Brien.

At least 19 recordsLinked to original sources
PubMed2006

Insurgence of Fusarium keratitis associated with contact lens wear.

OBJECTIVE: To describe the clinical presentation and course of patients who developed keratitis due to Fusarium while wearing nontherapeutic soft contact lenses. METHODS: A retrospective review of microbiologic records from January 1, 2004, through April 15, 2006, was performed, identifying all patients with corneal ulceration and a culture positive for Fusarium species. Medical records of 34 patients were reviewed for clinical characteristics, treatment regimens, and microbiologic features. RESULTS: The most common antimicrobial medications administered prior to Fusarium diagnosis were antibacterials in 31 of 34 patients. No distinct preponderance of any one brand of either contact lens or solution was identified. The microbiologic corneal cultures found Fusarium oxysporum in 20 cases, Fusarium solani in 3 cases, Fusarium species not further identifiable in 10 cases, and no growth in 1 case. Patients with a delayed onset of treatment had a tendency for prolonged treatment until cure. CONCLUSIONS: Fusarium has previously been an unusual organism in the etiology of infectious keratitis in the setting of nontherapeutic soft contact lens wear. A delay in proper diagnosis and intervention may contribute to a prolonged treatment course. The microbial spectrum of contact lens-related keratitis may be evolving with higher participation of Fusarium species compared with prior reports.

Adolescent↗
PubMed2006

Complications of sequential keratorefractive and vitreoretinal surgery.

We describe 2 complications of sequential keratorefractive and vitreoretinal surgery not previously reported. Epithelial ingrowth occurred in 1 patient who experienced laser in situ keratomileusis flap dehiscence and replacement during vitreoretinal surgery. In the second patient, a flap could not be created with a microkeratome or a femtosecond laser because of anatomical changes from previous vitreoretinal surgery. Anatomic repair of the vitreoretinal pathology and completion of keratorefractive surgery with good visual outcomes were achieved in both patients. Flap stability should be an important operative consideration for vitreoretinal surgeons; patients may have to be informed of the risk for and possible subsequent complications of iatrogenic flap dehiscence. Refractive surgeons operating on patients after vitreoretinal surgery may encounter difficulty creating a LASIK flap even with a femtosecond laser and may need to consider other keratorefractive options.

Aged↗
PubMed2006

Dysfunctional tear syndrome: a Delphi approach to treatment recommendations.

PURPOSE: To develop current treatment recommendations for dry eye disease from consensus of expert advice. METHODS: Of 25 preselected international specialists on dry eye, 17 agreed to participate in a modified, 2-round Delphi panel approach. Based on available literature and standards of care, a survey was presented to each panelist. A two-thirds majority was used for consensus building from responses obtained. Treatment algorithms were created. Treatment recommendations for different types and severity levels of dry eye disease were the main outcome. RESULTS: A new term for dry eye disease was proposed: dysfunctional tear syndrome (DTS). Treatment recommendations were based primarily on patient symptoms and signs. Available diagnostic tests were considered of secondary importance in guiding therapy. Development of algorithms was based on the presence or absence of lid margin disease and disturbances of tear distribution and clearance. Disease severity was considered the most important factor for treatment decision-making and was categorized into 4 levels. Severity was assessed on the basis of tear substitute requirements, symptoms of ocular discomfort, and visual disturbance. Clinical signs present in lids, tear film, conjunctiva, and cornea were also used for categorization of severity. Consensus was reached on treatment algorithms for DTS with and without concurrent lid disease. CONCLUSION: Panelist opinion relied on symptoms and signs (not tests) for selection of treatment strategies. Therapy is chosen to match disease severity and presence versus absence of lid margin disease or tear distribution and clearance disturbances.

Algorithms↗
PubMed2005

Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients.

PURPOSE: To measure the achievable perioperative aqueous concentration of the commercially available topically administered fourth generation fluoroquinolones, moxifloxacin 0.5% ophthalmic solution, and gatifloxacin 0.3% ophthalmic solution, and to correlate this concentration with the agents' biological efficacy in the aqueous humor of patients undergoing routine cataract surgery. DESIGN: Prospective, randomized, parallel, double-masked, clinical trial. PARTICIPANTS: Fifty patients undergoing cataract extraction. METHODS: Patients (n = 25) were given perioperative topical moxifloxacin 0.5% or topical gatifloxacin 0.3% (n = 25). One drop of antibiotic was administered every 10 minutes for 4 doses beginning 1 hour prior to surgery. Aqueous humor was sampled via paracentesis and antibiotic concentrations were determined using validated high performance liquid chromatography (HPLC) procedures. Dilution analyses were performed to determine the biological efficacy of the agents in the aqueous against Staphylococcus epidermidis, the most common cause of postcataract endophthalmitis. MAIN OUTCOME MEASURES: Aqueous humor antibiotic concentrations were measured using HPLC and microdilution bioassay techniques. Biological activity was measured as minimal inhibitory dilution and minimal bactericidal dilution. RESULTS: Aqueous humor concentrations for moxifloxacin via HPLC analysis were 1.80 (+/-1.21) microg/ml, whereas those for gatifloxacin were 0.48 (+/-0.34) microg/ml. This 3.8-fold difference in aqueous humor antibiotic concentrations was statistically significant (P = 0.00003). Similarly, the biological dilution analysis of the aqueous humor samples showed that moxifloxacin attained an estimated activity of 2.1 microg/ml, whereas the gatifloxacin activity was approximately 0.4 mug/ml, which represented a 4.9-fold difference. CONCLUSIONS: This study demonstrated that after topically administered perioperative antibiotics with cataract surgery, moxifloxacin 0.5% ophthalmic solution achieved a statistically significantly higher concentration in aqueous humor compared with gatifloxacin (P = 0.00003). Results from the broth dilution analysis showed that moxifloxacin 0.5% was biologically more active against S. epidermidis than gatifloxacin 0.3% in aqueous humor after topical application. There were no adverse events reported, and incision wounds healed quickly and as expected.

Administration, Topical↗
PubMed2005

A spontaneous mutation affects programmed cell death during development of the rat eye.

We have discovered a spontaneous mutation in the Sprague-Dawley rat with a novel eye phenotype that we have named Nuc1. The Nuc1 mutation behaves as a single semi-dominant locus with an intermediate phenotype in the heterozygotes. Heterozygotes exhibit nuclear cataracts. Homozygous Nuc1 rats are fully viable and have microphthalmia, retinal abnormalities and disruption of lens structure shortly before birth. The homozygous mutant shows no obvious pathology outside of the eye, indicating that the mutation is highly eye specific in its effects. An unusual feature of the mutation is that it prevents the normal programmed loss of nuclei from lens fiber cells, but does not affect the loss of other organelles. TUNEL, light, and electron microscopic studies show normal intact nuclei in lens fibers, in contrast to many other models with degenerate nuclei and unlike normal lenses where no such nuclei remain. The beaded filament protein, filensin, is down-regulated in fibers of Nuc1, while heat shock cognate 70 is up-regulated. Homozygous retinas are thicker than normal, and TUNEL labeling indicates roughly half the number of apoptotic cells compared to a wild-type retina. The transient layer of Chievitz persists in adult Nuc1 retina, indicative of delayed development. Hence, Nuc1 is a novel mutation that could be an eye-specific regulator of apoptosis.

Animals↗
PubMed2005

Excimer laser surgery for correction of ametropia after cataract surgery.

PURPOSE: To review the cases of patients who had excimer laser refractive surgery to correct unintentional or undesired ametropia after cataract extraction with intraocular lens (IOL) implantation. SETTING: Wilmer Laser Vision Correction Center, Wilmer Eye Institute, Baltimore, Maryland, USA. METHODS: In this retrospective noncomparative review of consecutive cases, the Wilmer Laser Vision Correction Center's database was searched for patients who had laser in situ keratomileusis or photorefractive keratectomy to correct ametropia after cataract extraction with IOL implantation. RESULTS: Using the Visx Star excimer laser system (Visx, Inc.), 11 procedures were performed in 11 eyes of 10 patients a mean of 47 months (range 2 to 216 months) after cataract extraction with IOL implantation. Except for 1 patient with a silicone plate lens, all patients received 3-piece poly(methyl methacrylate) lenses. The mean age at time of excimer treatment was 75 years (range 70 to 81 years). Before laser surgery, the mean spherical equivalent of patient eyes was -3.76 diopters (D) +/- 2.50 (SD) (range -6.50 to +0.75 D), spherical refraction ranged from -9.00 D to plano, and the highest cylindrical refraction was +5.50 D. At last follow-up (mean 12.2 months; range 1 to 38 months), the mean manifest spherical equivalent was -0.88 +/- 1.43 D (range -2.75 to +2.13 D). Changes in mean manifest spherical equivalent were highly significant (P = .03, Wilcoxon signed rank test for paired values). There was no difference between targeted and achieved postoperative refraction (P = .34, Wilcoxon test). Increasing age was correlated with a hyperopic shift (r = 0.525, P = .05). All patients were satisfied with their final uncorrected visual acuity (UCVA), which improved in every case. Except for 1 patient in whom an epiretinal membrane developed, best spectacle-corrected visual acuity remained unchanged or improved. CONCLUSIONS: In this series of patients, who were a few decades older than the typical excimer laser candidate, laser refractive surgery was a safe, effective, and predictable method to correct ametropia after cataract extraction with IOL implantation. It may be a viable, noninvasive alternative to intraocular surgery, which has potential complications. Although satisfactory for all patients, final UCVA was not as high as that reported in laser refractive surgery patients in general, and this result may be because of prior cataract extraction with IOL implantation or increased age.

Aged↗
PubMed2005

High interocular corneal symmetry in average simulated keratometry, central corneal thickness, and posterior elevation.

PURPOSE: The purpose of this study was to assess interocular corneal symmetry in average simulated keratometry, corneal thickness, and posterior corneal elevation. METHODS: This retrospective analysis included data from scanning slit topography (Orbscan II; Bausch and Lomb, Rochester, NY) on 242 eyes from 121 consecutive patients undergoing standard evaluation for consideration of elective laser vision correction. The symmetry between the right and left eye in average simulated keratometry, minimum central corneal thickness, and posterior corneal elevation was assessed by comparative data analysis. RESULTS: Simulated keratometry ranged from 39.9 to 48.6 D. The interocular difference in average simulated keratometry was 0.47 D (standard deviation [SD] 0.43). The interocular Pearson correlation coefficient for average simulated keratometry was 0.90 (p < 0.001). The range of minimum corneal thickness was 432 to 628 microm. The interocular Pearson correlation coefficient for minimum central corneal thickness was 0.95 (p < 0.001). Right and left eye minimum corneal thickness differed by an average 8 microm (SD 7). The range of posterior elevation was -4 to 54 microm. The average difference in posterior corneal elevation between the right and left eye was 6 microm (SD 5). The interocular Pearson correlation coefficient for posterior corneal elevation was 0.72 (p < 0.001). The average posterior elevation was 19 microm (SD 11). CONCLUSIONS: Although a wide range of values exists in simulated keratometry, minimum corneal thickness, and posterior corneal elevation, interocular symmetry in all these parameters was very high in this group of consecutive patients. Asymmetry of these interocular parameters may warrant repeat clinical testing for accuracy and may predict corneal abnormalities. Normative data on posterior cornea elevation is presented. This study points out potentially clinically important high interocular corneal symmetry data in simulated keratometry, corneal thickness, and posterior corneal elevation.

Contact Lenses↗
PubMed2005

Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery.

A prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10 min for four doses beginning 1 h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (p < 0.01) than those for gatifloxacin.

Administration, Topical↗
PubMed2004

Downregulation of class II transactivator (CIITA) expression by synthetic cannabinoid CP55,940.

Cannabinoid receptors are known to be expressed in microglia; however, their involvement in specific aspects of microglial immune function has not been demonstrated. Many effects of cannabinoids are mediated by two G-protein coupled receptors, designated CB1 and CB2. We have shown that the CB1 receptor is expressed in microglia that also express MHC class II antigen (J. Neuroimmunol. 82 (1998) 13-21). In our present study, we have analyzed the effect of cannabinoid agonist CP55,940 on MHC class II expression on the surface of IFN-gamma induced microglial cells by flow cytometry. CP55,940 blocked the class II MHC expression induced by IFN-gamma. It has been shown that the regulation of class II MHC genes occurs primarily at the transcriptional level, and a non-DNA binding protein, class II transactivator (CIITA), has been shown to be the master activator for class II transcription. We find that mRNA levels of CIITA are increased in IFN-gamma induced EOC 20 microglial cells and that this increase is almost entirely eliminated by the cannabinoid agonist CP55,940. These data suggests that cannabinoids affect MHC class II expression through actions on CIITA at the transcriptional level.

Animals↗
PubMed2004

Treatment of experimental bacterial keratitis with topical trovafloxacin.

OBJECTIVE: To investigate the therapeutic role of trovafloxacin mesylate, a newer-generation fluoroquinolone with an expanded spectrum of activity, in the treatment of experimental bacterial keratitis. METHODS: Susceptibility studies were performed on various strains of ocular isolates to determine the minimum inhibitory concentration (MIC) of trovafloxacin compared with ciprofloxacin and ofloxacin, using the E-test method. Pharmacokinetic studies were performed by a single topical administration of trovafloxacin to rabbit eyes with either an intact or denuded corneal epithelium. Aqueous humor, vitreous, and corneal concentrations of trovafloxacin were determined at different time points. Experimental bacterial keratitis studies were performed in rabbit eyes. Three identical studies were conducted using Staphylococcus aureus, Streptococcus pneumoniae, or Pseudomonas aeruginosa. Therapy groups included 0.5% trovafloxacin, 0.3% ciprofloxacin, 0.3% ofloxacin, and isotonic sodium chloride solution. After 12 hours of drops administration, corneas were excised, homogenized, and serially plated. The main outcome measure was quantitative bacteriologic analysis for residual colony-forming units. RESULTS: In vitro susceptibility study findings indicated that the MIC of trovafloxacin was significantly lower than the MIC of ciprofloxacin and ofloxacin for S. aureus, S. pneumoniae, and Haemophilus influenzae, lower than the MIC of ciprofloxacin and ofloxacin for Staphylococcus epidermidis, and intermediate between ciprofloxacin and ofloxacin for P. aeruginosa. Pharmacokinetic studies showed a significant concentration of trovafloxacin in the treated corneas, especially in eyes with a denuded epithelium. All serum samples had undetectable trovafloxacin concentrations. Experimental keratitis studies showed a statistically significant decrease of colony-forming units in trovafloxacin-treated eyes in the S. aureus model and a similar decrease in the S pneumoniae and P aeruginosa models. CONCLUSIONS: Topical 0.5% trovafloxacin proved to be an effective ocular medication for the therapy of gram-positive and gram-negative keratitis. Clinical Relevance Trovafloxacin may provide an excellent therapeutic alternative in bacterial keratitis.

Administration, Topical↗
PubMed2004

Comparative efficacy of topical gatifloxacin with ciprofloxacin, amikacin, and clarithromycin in the treatment of experimental Mycobacterium chelonae keratitis.

OBJECTIVE: To determine the comparative efficacy of topical gatifloxacin with ciprofloxacin, fortified amikacin, and clarithromycin against Mycobacterium chelonae keratitis in an animal model. METHODS: Experimental M chelonae keratitis was induced via intrastromal inoculation in a rabbit model. Thirty-five rabbits were randomly divided into 5 groups and each group was treated hourly for 12 hours with topical 0.9% balanced salt solution, 0.3% gatifloxacin, 0.3% ciprofloxacin hydrochloride, a combination of topical fortified amikacin sulfate (50 mg/mL) and clarithromycin (10 mg/mL), or a triple combination of topical 0.3% gatifloxacin, fortified amikacin sulfate (50 mg/mL), and clarithromycin (10 mg/mL). Antibacterial efficacy of each regimen was determined by quantitative bacteriologic analysis. RESULTS: Treatment with 0.3% gatifloxacin or the triple combination of 0.3% gatifloxacin, topical fortified amikacin sulfate (50 mg/mL), and clarithromycin (10 mg/mL) reduced the number of mycobacterial organisms more significantly than the controls that were treated with a topical balanced salt solution (both P<.001). Therapy with 0.3% gatifloxacin was more effective than 0.3% ciprofloxacin alone (P<.001) and demonstrated synergy by enhancing the efficacy of the combination of fortified amikacin (50 mg/mL) and clarithromycin (10 mg/mL) (P<.001). Neither 0.3% ciprofloxacin nor the combination of fortified amikacin (50 mg/mL) and clarithromycin (10 mg/mL) demonstrated a significant difference in activity against mycobacteria compared with the topical balanced salt solution. CONCLUSION: These results suggest that topical 0.3% gatifloxacin ophthalmic solution can be a new initial treatment agent against M chelonae keratitis.Clinical Relevance Topical gatifloxacin 0.3% may provide an initial alternative in therapy of M chelonae keratitis.

Administration, Topical↗
PubMed2004

The effect of nerve growth factor on corneal sensitivity after laser in situ keratomileusis.

OBJECTIVE: To determine if topically administered nerve growth factor (NGF) plays a role in accelerating the recovery of corneal sensitivity after laser in situ keratomileusis (LASIK). METHODS: A prospective double-masked study comparing the effect of topical NGF with balanced salt solution on corneal sensitivity after LASIK in rabbits. Preoperative and postoperative corneal sensitivities were assessed using an esthesiometer (Cochet-Bonnet esthesiometer). RESULTS: Eyes that were treated with topical NGF demonstrated an earlier and faster recovery of corneal sensitivity after LASIK (P =.007). A statistically significant difference in corneal sensitivity was found between the topical NGF and control group postoperatively at 2 (P =.01), 3 (P =.03), and 4 (P =.03) weeks. CONCLUSION: Topically administered NGF may play a significant role in accelerating corneal reinnervation after LASIK. Clinical Relevance Our results showed that topical NGF had beneficial effects in the early recovery of corneal sensitivity after LASIK. Nerve growth factor can be a new therapeutic approach for dry eye syndrome after LASIK.

Acetates↗
PubMed2004

Outcome of second surgery in LASIK cases aborted due to flap complications.

PURPOSE: To describe the technique and timing of second refractive surgery after aborted laser in situ keratomileusis (LASIK) due to intraoperative flap complication and determine the final visual outcome. SETTING: Outpatient ambulatory laser vision correction centers. METHODS: This retrospective noncomparative case series included 16 patients (16 eyes) who had a second refractive surgery after initial LASIK surgery was aborted because of a flap complication. Charts were reviewed with attention to initial preoperative data, intraoperative details of the aborted LASIK, postoperative examination, possible causes of the flap complication, timing and technique of second refractive surgery, and final visual outcome. RESULTS: Causes of the aborted LASIK were identified in 13 of 16 eyes (81.2%) and included eye squeezing (5 eyes), loss of suction or machine failure (5 eyes), steep corneas (2 eyes), and learning curve of the surgeon (1 eye). The mean time until the second surgery was 135 days (range 49 to 372 days). Repeat flaps were created deeper and larger than the initially attempted flaps when possible. No patient had a final uncorrected visual acuity (UCVA) worse than 20/30 after the second surgery. Two eyes (12.5%) lost 1 line of best spectacle-corrected visual acuity. CONCLUSION: A planned delayed reoperation after sufficient corneal healing following an intraoperative flap complication can result in satisfactory recovery of UCVA.

Adult↗
PubMed2004

Survey of complications and recommendations for management in dissatisfied patients seeking a consultation after refractive surgery.

PURPOSE: To review complications associated with and management options for dissatisfied patients seeking a consultation after refractive surgery performed elsewhere. SETTING: Refractive Eye Surgery Center, The Wilmer Institute, Lutherville, Maryland, USA. METHODS: In this retrospective review, charts of consecutive dissatisfied patients who sought a refractive consultation between June 1999 and January 2003 after refractive surgery performed elsewhere were reviewed and the following parameters were analyzed: visual acuity (uncorrected and best spectacle corrected), prior manifest refraction, complications, and recommendations. The subjective complaints, complications, and visual acuity were reviewed, and the associated historical or visual risk factors as well as treatment options were analyzed. RESULTS: One hundred sixty-one eyes in 101 patients with ocular complaints were identified. One hundred thirty-four eyes (83.2%) had had laser in situ keratomileusis; 22 eyes, photorefractive keratectomy; 4 eyes, radial keratotomy; and 1 eye, laser thermokeratoplasty. The most common subjective complaints were blurred distance vision (59.0%), glare and night-vision disturbances (43.5%), and dry eyes (21.1%). The most common complications were overcorrection (30.4%), irregular astigmatism (29.8%), dry eyes (29.8%), glare (26.1%), difficulty with night driving (16.7%), and corneal haze (16.7%). The most common cause identified in eyes with best spectacle-corrected visual acuity worse than 20/40 was irregular astigmatism (10 of 18 eyes [55.5%]). The most common recommendation for management was medical treatment or observation (68.3%). Medical therapies recommended included lubrication, punctal plugs, topical and systemic pharmaceutical agents to modulate ocular surface, spectacles, and contact lenses. Keratoplasty (lamellar or penetrating) was recommended in 4 patients (4 eyes [2.5%]). The diagnoses included corneal ectasia in 3 eyes and severe flap complication with irregular astigmatism in 1 eye. Nine patients (5.6% eyes) required nonkeratoplasty surgery. In other patients, waiting for advances in technology, including wavefront-guided customized retreatment, was recommended. CONCLUSIONS: A spectrum of complications associated with refractive surgery may result in patient dissatisfaction. Proper patient selection, prevention strategies, and prompt diagnosis and medical or surgical intervention may be beneficial in managing complications and improving patient satisfaction.

Adult↗
PubMed2004

Improvement in best corrected visual acuity in amblyopic adult eyes after laser in situ keratomileusis.

PURPOSE: To evaluate improvement in best spectacle-corrected visual acuity (BSCVA) after laser in situ keratomileusis (LASIK) in adult patients with amblyopia. SETTING: Refractive Eye Surgery Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. METHODS: The charts of consecutive patients with a diagnosis of amblyopia at the time of refractive evaluation who had LASIK were reviewed retrospectively. The preoperative and postoperative uncorrected visual acuity (UCVA) and BSCVA were analyzed. RESULTS: Twenty-one eyes of 19 patients were identified as having amblyopia and LASIK surgery. Eight patients (42.1%) were diagnosed with amblyopia only, 6 patients (31.6%) had anisometropic amblyopia, 4 patients (21.1%) had strabismic amblyopia, and 1 patient (5.2%) had anisometropic and strabismic amblyopia. Eleven eyes (52.4%) had myopic astigmatism, 7 eyes (33.3%) were hyperopic, and 3 eyes (14.3%) had mixed astigmatism. Seven eyes (33.3 %) experienced more than a 1-line improvement in postoperative UCVA compared with the preoperative BSCVA. Nine eyes (42.8%) experienced more than a 1-line improvement in postoperative BSCVA compared with the preoperative BSCVA. The BSCVA was unchanged in 11 eyes (52.4%) and was worse by 2 lines in 1 eye (4.8%). CONCLUSION: After LASIK, the postoperative BSCVA was better than preoperatively in 42.8% of eyes with a history of amblyopia and the postoperative UCVA was better than the preoperative BSCVA in 33.3%.

Adult↗