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Biomedical subjects

James P McCulley

Publications and source records attributed to James P McCulley.

At least 19 recordsLinked to original sources

Updates in Acanthamoeba keratitis.

PURPOSE: Acanthamoeba keratitis is a potentially blinding microbial disease that has been increasing in incidence during the past two decades. Prognosis of this serious disease had been dismal, but improvement in diagnosis, a better understanding of the natural course of the disease, and recent introduction of multiple and effective therapeutic agents have resulted in improvement of visual outcomes. METHODS: A review of literature pertaining to Acanthamoeba keratitis. RESULTS: Contact lens wear and exposure to contaminated water sources remain the most important risk factors; however, in vivo confocal microscopy and improved biomicroscopic screening have proven instrumental in accurate early diagnosis. Complications of Acanthamoeba keratitis include dacryoadenitis, corneal melting and scarring, severe secondary glaucoma, cataract, and chronic anterior segment inflammation that can rarely lead to reactive blinding retinal ischemia. Combination chemotherapeutic agents have been shown to be more effective than monotherapy, whereas rehabilitative surgery such as penetrating keratoplasty is best performed on a quiet eye free of ocular inflammation and with no residual amoebae. CONCLUSIONS: Increased suspicion by clinicians for Acanthamoeba and confocal microscopy have allowed more rapid and accurate diagnosis; treatment with multiple antiamoeba drugs is essential to disease resolution. Provided there are no residual amoebae after treatment, penetrating keratoplasty has been successful in visual rehabilitation. Secondary glaucoma occurs frequently and may require drainage procedures for control of intraocular pressure. Posterior complications are rare but may lead to ischemic retinitis.

Acanthamoeba↗

Severe reactive ischemic posterior segment inflammation in acanthamoeba keratitis: a new potentially blinding syndrome.

OBJECTIVE: To describe a newly recognized clinical syndrome in Acanthamoeba keratitis consisting of severe reactive ischemic posterior segment vascular inflammation. DESIGN: Noncomparative, retrospective, single-institution observational case series. PARTICIPANTS: Five eyes of 5 patients with Acanthamoeba keratitis. METHODS: A retrospective review of the records of patients diagnosed with Acanthamoeba keratitis between January 1, 1995, and December 1, 2005, was conducted to identify those who underwent eventual enucleation. Five enucleated eyes of 118 eyes with Acanthamoeba keratitis were identified. MAIN OUTCOME MEASURES: History, clinical examination results, available laboratory study results, and histopathologic examination results. RESULTS: Histopathologic examination showed Acanthamoeba cysts in the cornea in 4 eyes, whereas it failed to demonstrate amebic cysts or trophozoites in the posterior segment of all eyes studied and unexpectedly revealed chronic chorioretinal inflammation with perivascular lymphocytic infiltration and diffuse neuroretinal ischemia in 4 of 5 eyes. Retinal artery thrombosis was present in 3 of the 4 involved eyes, and central retinal artery and vein thrombosis was found in 1 eye. Hematologic studies in 3 patients showed abnormal anticardiolipin antibody levels in 1 patient and factor V Leiden deficiency in another. CONCLUSIONS: Prolonged Acanthamoeba keratitis can result in a severe sterile ischemic posterior segment inflammation that is potentially blinding, especially in patients with underlying hypercoagulation disorders.

Acanthamoeba Keratitis↗

Proposed new classification scheme for chemical injury to the human eye.

PURPOSE: Various ocular alkali burn classification schemes have been published and used to grade human chemical eye injuries for the purpose of identifying treatments and forecasting outcomes. The ILSI chemical eye injury classification scheme was developed for the additional purpose of collecting detailed human eye injury data to provide information on the mechanisms associated with chemical eye injuries. This information will have clinical application, as well as use in the development and validation of new methods to assess ocular toxicity. METHODS: A panel of ophthalmic researchers proposed the new classification scheme based upon current knowledge of the mechanisms of eye injury, and their collective clinical and research experience. Additional ophthalmologists and researchers were surveyed to critique the scheme. The draft scheme was revised, and the proposed scheme represents the best consensus from at least 23 physicians and scientists. RESULTS: The new scheme classifies chemical eye injury into five categories based on clinical signs, symptoms, and expected outcomes. Diagnostic classification is based primarily on two clinical endpoints: (1) the extent (area) of injury at the limbus, and (2) the degree of injury (area and depth) to the cornea. CONCLUSIONS: The new classification scheme provides a uniform system for scoring eye injury across chemical classes, and provides enough detail for the clinician to collect data that will be relevant to identifying the mechanisms of ocular injury.

Animal Testing Alternatives↗

Ocular surface restoration using non-surgical transplantation of tissue-cultured human amniotic epithelial cells.

PURPOSE: To assess the effect of tissue-cultured human amniotic epithelial cells (AECs) in restoring the ocular surface, transplanted using a collagen shield seeded with AECs supported by a soft contact lens. DESIGN: Prospective interventional single-institutional case series with crossover controls. METHODS: Three eyes in three patients were identified with persistent corneal epithelial defects (PEDs) refractory to medical therapy. Two cases were secondary to neurotrophic keratopathy, while one case was attributable to longstanding alkali injury. AECs were isolated from serologically screened donor human placenta, seeded onto collagen corneal shields, and incubated in tissue culture medium for 7 days. These collagen shields were placed over the PED and supported by an overlying soft contact lens. The collagen shields dissolved by 72 hours, and the contact lenses were removed after this time. This cycle was repeated every week until healing was achieved. As a crossover control, collagen shields without AECs were placed in the same eye 1 week before placing collagen shields containing AECs. The PED was assessed by vital staining and slit-lamp color photography. RESULTS: The PEDs had a mean duration of 4 months and involved 20% to 37% of the corneal surface area, one case secondary to longstanding alkali injury and two cases attributable to neurotrophic keratopathy. No change in PED size was observed in those control eyes receiving collagen shields without AECs. Complete resolution of the PED was seen after two cycles of AEC-seeded collagen shield in one case, and four cycles in two cases, from 7 to 12 weeks following treatment in all patients. No loss of visual acuity was seen and clinical improvement was maintained in all cases, with a mean follow-up of 6.3 months. CONCLUSIONS: Nonsurgical transplantation of tissue-cultured AECs on a collagen shield provides a promising approach to restoring the ocular surface in cases of PED.

Adult↗

Correlations in a change in aqueous tear evaporation with a change in relative humidity and the impact.

PURPOSE: To establish scientific relationship between relative humidity (RH) and aqueous tear evaporation to elucidate possible significance of this relationship in normals and aqueous tear deficiency patients. DESIGN: Prospective experimental laboratory study. METHODS: Ocular surface evaporation was determined using evaporometry and calculated for two ranges of RH, 25% to 35%, and 35% to 45% in a randomized clinical patient population. RESULTS: Average evaporative rate in the higher humidity range was between 0.029 +/- 0.009 through 0.043 +/- 0.016 microl/cm2/min. At lower humidity, range was between 0.044 +/- 0.013 through 0.058 +/- 0.018 microl/cm2/min. Differences in the corresponding evaporative rates were statistically significant (between P < .003 through P < .043) for each analysis. CONCLUSIONS: A decrease of 10% RH resulted in an average difference of between 28.33% to 59.42% increase in evaporation. The increase in evaporation at lower humidity has significant clinical implications for patients with aqueous deficient dry eyes, and possibly those undergoing laser-assisted in situ keratomileusis (LASIK).

Diagnostic Techniques, Ophthalmological↗

Comparative higher-order aberration measurement of the LADARWave and Visx WaveScan aberrometers at varying pupil sizes and after pharmacologic dilation and cycloplegia.

PURPOSE: To compare higher-order aberration (HOA) measurements of LADARWave and Visx WaveScan aberrometers, to test the validity of the peripheral wavefront data, and to evaluate the effect of pharmacologic dilation and mild cycloplegia. METHODS: Thirty-three myopic eyes of 17 volunteers were enrolled and had the ocular HOAs measured and analyzed with varying pupil diameters (PD) controlled by a tunable light intensity source and after instillation of tropicamide 1% and phenylephrine 2.5%. RESULTS: Higher-order aberrations increased with PD and optical zone (OZ), especially an OZ between 6.0 mm and 6.5 mm. Spherical aberration increased the most, followed by coma, then trefoil and secondary astigmatism. Measurement differences were observed between LADARWave and WaveScan at an OZ of 6.0 mm, although measurement correlations between the 2 machines were high. In the case of the WaveScan, when PD = OZ (6.0 mm), the spherical aberration and, to a less extent, the coma data differed from those obtained with larger PDs and the same OZ. In the case of the LADARWave, at an OZ of 6.0 mm, the HOAs measured in eyes with physiologic pupils were similar to those in pharmacologically dilated pupils when the physiologic pupil center was taken as the reference. CONCLUSIONS: There were detectable measurement differences between LADARWave and Visx WaveScan. Ensuring that the PD is at least 0.5 mm larger than the desired OZ is very important. Dilation and mild cycloplegia did not clinically affect the wave measurement magnitude or pattern.

Adult↗

Confocal assessment of the corneal response to intracorneal lens insertion and laser in situ keratomileusis with flap creation using IntraLase.

PURPOSE: To assess the response of the cornea to hydrogel intracorneal lens (ICL) insertion or laser in situ keratomileusis (LASIK) with IntraLase (IntraLase Corp.) at the cellular level. SETTING: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. METHODS: Twenty patients (29 eyes) were evaluated by in vivo confocal microscopy 1 to 6 months postoperatively: 20 eyes had LASIK with flap creation by IntraLase, and 9 eyes had ICL insertion (8 following IntraLase). RESULTS: For LASIK with IntraLase, keratocyte activation and/or interface haze was detected in 8 of 20 eyes. The remaining eyes had interface particles but no cell activation. Keratocyte activation was generally limited to a few cell layers adjacent to the interface. However, 2 patients exhibited multiple layers of activation and increased extracellular matrix (ECM) reflectivity (haze) surrounding the interface by confocal microscopy. Both patients also had clinical haze and photophobia. For ICLs, following insertion, 5 of 9 eyes had activated keratocytes adjacent to the implant surfaces. The largest amount of cell activation and ECM haze detected by confocal microscopy was in 2 patients with significant clinical haze. Structures with an epithelioid morphology were detected on some implant surfaces. Epithelial thickness was 33.3 microm +/- 2.3 (SD) in the ICL eyes and 49.2 +/- 6.5 microm in the LASIK with IntraLase eyes. CONCLUSIONS: Both LASIK with IntraLase and ICL insertion following IntraLase induced keratocyte activation, which may underlie clinical observations of haze in some patients. Intracorneal lens implant also induced thinning of the overlying corneal epithelium.

Biocompatible Materials↗

Tandem scanning confocal corneal microscopy in the diagnosis of suspected acanthamoeba keratitis.

OBJECTIVE: To evaluate the role of in vivo corneal tandem scanning confocal microscopy (TSCM) in the definitive diagnosis of suspected Acanthamoeba keratitis (AK). DESIGN: Noncomparative interventional single-institution case series. METHOD: A retrospective case review of patients consecutively referred with suspected AK and undergoing corneal TSCM was performed. RESULTS: A total of 63 cases that met the inclusion criteria for the study were referred for diagnostic evaluation. Tandem scanning confocal microscopy demonstrated Acanthamoeba cysts/trophozoites in 54 cases and fungal hyphae in 2, whereas 1 case was positive for both Acanthamoeba and fungus. Culture of the cornea or contact lenses was carried out in 35 cases, 9 of which were positive for Acanthamoeba. Six of the TSCM-positive cases also underwent corneal biopsy, being positive for Acanthamoeba in only 2. Six patients were negative for Acanthamoeba on TSCM, the etiology being fungal in 1 case, as shown by subsequent culture. One patient was positive on culture for Acanthamoeba but falsely negative by TSCM, which was limited by poor cooperation during the examination. Two cases initially masqueraded as Acanthamoeba keratitis but showed fungus on TSCM. Mean follow-up was 14 months. CONCLUSION: In vivo corneal TSCM can establish the diagnosis of Acanthamoeba keratitis rapidly and noninvasively, particularly when conventional microbiology is inconclusive.

Acanthamoeba Keratitis↗

Evaluation of intrastromal lipid deposits after intacs implantation using in vivo confocal microscopy.

PURPOSE: To assess the structure and location of intrastromal lipid deposits after implantation of Intacs by using in vivo confocal microscopy. METHODS: Seven eyes of six patients were examined by in vivo confocal microscopy 5 years (n = 6) or 2 months (n = 1) after uncomplicated implantation of Intacs for the correction of mild myopia. Selected images from all corneal layers were qualitatively evaluated for structural changes, with special attention paid to areas surrounding the Intacs implants. RESULTS: In the peripheral cornea of eyes examined 5 years after surgery, epithelial and endothelial cell layers appeared normal. Tandem scanning confocal microscopy showed stromal haze surrounding the implants in all eyes examined, but no keratocyte activation was seen. Reflective amorphous or crystalline structures consistent with lipid deposition were detected in all eyes with long-term implantation of Intacs. Deposits were localized to the inner and outer edges of Intacs segments and to the region anterior to the implant. Confocal microscopy did not show any deposits in the eye examined 2 months after surgery, although the region anterior to the implant appeared hazy and edematous. Areas central to the implant appeared normal in all eyes. CONCLUSIONS: The mechanical and physiologic stresses introduced by the implantation of Intacs lead to the accumulation of lipid deposits in the extracellular matrix. By using in vivo confocal microscopy, the location and structure of these deposits can be determined.

Adult↗

Results of penetrating keratoplasty for visual rehabilitation after Acanthamoeba keratitis.

PURPOSE: To assess the results of penetrating keratoplasty in quiet eyes after resolution of Acanthamoeba keratitis. DESIGN: A retrospective interventional case series. METHODS: Penetrating keratoplasty was undertaken in 13 eyes of 13 patients with an average age of 29 +/- 13 years and a history of Acanthamoeba keratitis that was diagnosed by culture and/or confocal microscopy between January 1995 and September 2004. All eyes were observed for at least 3 months (average, 5 months) after the discontinuation of antiamebic therapy that had been administered for at least 4.5 months. In vivo confocal microscopy was used to ensure that no residual amoeba were present before the operation. Two keratoplasties were combined with a valve insertion; five keratoplasties were combined with cataract extraction, and one keratoplasty was preceded by a ciliary laser ablation. RESULTS: Postoperative best-corrected visual acuity ranged from 20/40 to 20/15, with the exception of one eye with advanced glaucoma that did not improve from a preoperative vision of light perception. No eye experienced rejection or amoebic recurrences, and 12 grafts remained clear throughout the follow-up period (8 months to 9 years; median, 23 months). One graft failed at 4 months because of uncontrolled glaucoma. The eye was regrafted, and the graft remained clear during the 28 months of follow-up evaluation. Two eyes with preoperatively diagnosed glaucoma needed subsequent surgery to control their intraocular pressure. CONCLUSION: Penetrating keratoplasty for visual restoration after Acanthamoeba keratitis appears to have an excellent long-term prognosis, provided amoebic infection has resolved and concurrent glaucoma is controlled.

Acanthamoeba↗

Hyperopic laser in situ keratomileusis in eyes with previous radial keratotomy.

PURPOSE: To assess the safety and efficacy of hyperopic laser in situ keratomileusis (LASIK) in eyes with previous radial keratotomy (RK). SETTING: Zale Lipshy University Hospital Laser Center for Vision, University of Texas Southwestern Medical Center, Dallas, Texas, USA. METHODS: Thirty-eight eyes of 25 patients were treated with LASIK for secondary hyperopia after RK using a Visx Star S2, S3, S4, or LADARVision excimer laser. Retreatment was done in 7 eyes. The main outcome measures were manifest refraction spherical equivalent (MRSE), uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), predictability of treatment, and complications. RESULTS: Preoperative mean MRSE was +2.39 diopters (D) +/- 1.28 (SD) (range +0.87 to +6.00 D). At the last visit (25 eyes with minimum follow-up of 12 months, including retreatments), the mean follow-up was 23.3 +/- 7.3 months (range 12 to 34 months), the mean MRSE was +0.11 +/- 0.71 D, and the UCVA was 20/40 or better in 24 eyes (96%). Although no significant change in the mean MRSE was observed, the postoperative mean refractive cylinder showed a gradual increase over the follow-up period. No eye lost more than 2 lines of BSCVA. CONCLUSIONS: Laser in situ keratomileusis was a safe and effective treatment with good predictability for the correction of consecutive hyperopia after RK. Cylindrical errors were difficult to correct, and astigmatic correction tended to regress over time. Retreatments are safe when old flaps were relifted.

Adult↗

Immunosuppressive factors secreted by human amniotic epithelial cells.

PURPOSE: Amniotic membrane has been applied to the ocular surface to restore corneal function. The beneficial effect of amniotic membrane transplantation may be due to the immunosuppressive effects of amniotic epithelial cells. The purpose of this study was to determine whether amniotic epithelial cells (AECs) secrete anti-inflammatory and antiproliferative factors that affect the chemotaxis of neutrophils and macrophages and suppress both T- and B-cell proliferation in vitro. METHODS: Human amniotic cells were isolated from human amniotic membrane and cultured in vitro. The supernatants from AEC cultures were collected after 48 hours of incubation. Neutrophil and macrophage chemotactic activity was tested in the presence of AEC supernatant, using 24-well migration assay chambers. Lymphocyte proliferation was tested by H(3)-thymidine incorporation. Apoptosis was examined by caspase-3 and annexin V assays, and expression of cytokines was assessed by RT-PCR. RESULTS: AEC supernatant significantly inhibited the chemotactic activity of neutrophils and macrophages toward macrophage inflammatory protein (MIP)-2 (P < 0.05). The supernatant significantly reduced the proliferation of both T and B cells after mitogenic stimulation (P < 0.05). Caspase-3 assays revealed that the supernatant induced apoptosis of T and B cells, but not of corneal epithelial cells and liver cells. In contrast to lymphocytes, macrophages and neutrophils were resistant to apoptosis induced by AEC supernatant. The AECs expressed message for TNFalpha, Fas ligand (FasL), TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TGFbeta, and macrophage migration-inhibitory factor (MIF). However, AEC induction of apoptosis was inhibited (50%) by anti-FasL antibody but not by anti-TRAIL or anti-TNFalpha antibodies. Moreover, AEC supernatant inhibited macrophage migration in vitro. CONCLUSIONS: AECs secrete soluble factors that inhibit cells in both the innate and adaptive immune systems.

Amnion↗

The lipid layer of tears: dependent on meibomian gland function.

There is growing laboratory and clinical evidence implicating the meibomian glands of the eyelid as playing a critical role in the pathogenesis of various ocular surface disorders such as chronic blepharitis and dry eye. Meibomian glands produce a lipid material whose synthesis is dependent on factors such as stem cells, neurological stimulants and hormones. This lipid material is fluid, spreads easily, is a surfactant as well as an aqueous barrier, and must remain functional after a blink. Before delivery it can be modified by factors such as hormone abnormalities and even after delivery it may be modified by lipases produced by ocular bacteria.

Bacteria↗

Evaluation of the corneal effects of topical ophthalmic fluoroquinolones using in vivo confocal microscopy.

PURPOSE: To compare the effects of several fluoroquinolone antibiotics on the corneal epithelium and stroma using in vivo confocal microscopy. METHODS: Five antibiotic solutions were evaluated: 1) 0.3% ofloxacin (Oflox) solution with 0.005% benzalkonium chloride (BAC); 2) 0.3% gatifloxacin (Gati) solution with 0.005% BAC; 3) 0.3% ciprofloxacin (Cipro) solution with 0.006% BAC; 4) 0.5% levofloxacin (Levo) with 0.005% BAC; and 5) 0.5% moxifloxacin (Moxi) solution with no BAC. Preservative-free artificial tears (Tears) were used as a control. New Zealand white rabbits were used for this study (six per solution group). Ten days prior to exposure to any solution, central corneal epithelial thickness and stromal thickness were measured using in vivo confocal microscopy through focusing. Images of the superficial epithelium were also acquired. Both eyes of each rabbit then received one drop of the assigned solution six times the first day and then four times per day for 6 days. On day 7, in vivo confocal microscopy was repeated. RESULTS: A significant decrease in epithelial thickness was induced by 7 days of exposure to Levo, Gati, Oflox, and Cipro (P < 0.05, two-way repeated-measures ANOVA, Tukey test). Tears and Moxi, which do not contain BAC, did not induce significant changes in epithelial thickness. No significant changes in stromal thickness were detected (P = 0.266), and no keratocyte activation was observed for any of the solutions evaluated. CONCLUSION: We have previously used confocal microscopy to establish a correlation between epithelial thinning (due to superficial cell loss) and slight ocular irritation. The results of this study suggest that Moxi induces less damage to the corneal epithelium than other antibiotic solutions, perhaps because it does not contain BAC.

Animals↗

Hyperopic laser-assisted in situ keratomileusis results with LADARVision, Visx Star S2, and Visx Star S3.

PURPOSE: To compare the LADARVision (LV), Visx Star S3 (S3), and Visx Star S2 (S2) excimer lasers in the treatment of spherical hyperopia and hyperopic astigmatism with laser-assisted in situ keratomileusis. SETTING: A parallel, consecutive, three-surgeon, cohort comparison was performed at Zale Lipshy University Hospital, Laser Center for Vision, The University of Texas Southwestern Medical Center at Dallas, Texas for consecutive cases between January 2001 and October 2001. METHODS: Treatment outcomes of 105 hyperopic eyes with manifest refraction spherical equivalents of up to +6.50 diopters and astigmatism up to 3.75 diopters were compared. Forty-one eyes were treated with LV; 25 eyes were treated with S3; and 39 eyes were treated with S2. Outcome measures included uncorrected visual acuity, best spectacle-corrected visual acuity, predictability, and stability of treatments at 1 week and 1, 3, and 6 months. RESULTS: All three lasers were comparable in terms of refractive stability and predictability. The LV group had consistently better uncorrected visual acuities than did the S2 and S3 groups during the follow-up period. At 6 months, the LV group had statistically significantly better visual results than the S3 group at the 20/25 and 20/20 levels, whereas the only significant difference between the LV and S2 groups was at the 20/25 level. Better visual outcomes were achieved with S2 than with S3, but the differences were not statistically significant. No eye lost more than one line of best spectacle-corrected visual acuity. CONCLUSIONS: Predictability and stability of hyperopic laser-assisted in situ keratomileusis treatments with all three lasers were comparable. Visual results with LV at 6 months were statistically significantly better than those with S3 and S2.

Astigmatism↗