Ophthalmology
· 2006 Mar · PMID 16406537
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PURPOSE: To assess the asymmetry of 24-hour intraocular pressures (IOPs) between right and left eyes of untreated open-angle glaucoma (OAG) patients, and its influence on the monocular therapeutic trial. DESIGN: Experime...PURPOSE: To assess the asymmetry of 24-hour intraocular pressures (IOPs) between right and left eyes of untreated open-angle glaucoma (OAG) patients, and its influence on the monocular therapeutic trial. DESIGN: Experimental study with human patients. PARTICIPANTS: Forty-one subjects (40-78 years old) with untreated OAG. METHODS: Subjects were housed in a sleep laboratory for 24 hours. Intraocular pressures of both eyes were measured with a pneumatonometer every 2 hours with the patient in the sitting and supine positions from 7 am to 11 pm and in the supine position only from 11 pm to 7 am. Mean, peak, and trough IOPs were compared in right versus left eyes. The strength of association between right and left IOPs was assessed using coefficients of determination (R2). Validity of the monocular therapeutic trial was assessed by examining residual values from 2 linear regression models of right versus left IOP. MAIN OUTCOME MEASURES: Strength of association between IOPs of right and left eyes, and residual values from linear models of IOP. RESULTS: No statistically significant difference was found between mean, peak, or trough IOPs of right and left eyes over a 24-hour period. The strength of association for mean IOP was only moderate (R(2) = 0.421-0.623). Residual values of > or =3 mmHg were found in 14.0%+/-12.0% (mean +/- standard deviation) of IOP measurements for a symmetric linear regression model, and 8.5%+/-10.6% of IOP measurements for a best-fit linear regression model over 24 hours. CONCLUSIONS: In this group of untreated glaucoma patients, the strength of association between the right and left eye mean IOPs is only moderate. Residual values of > or =3 mmHg were more common using a symmetric model than with a best-fit model. The current method of performing monocular therapeutic trials in glaucoma patients is unreliable, but it may be possible to improve reliability by using several IOP measurements obtained at different times of the day instead of a single office measurement.
Ophthalmology
· 2006 Jan · PMID 16360208
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PURPOSE: To investigate the attachment of Acanthamoeba to first- and second-generation silicone hydrogel contact lenses, and to determine if patient wear or the presence of a bacterial biofilm coating affects attachment...PURPOSE: To investigate the attachment of Acanthamoeba to first- and second-generation silicone hydrogel contact lenses, and to determine if patient wear or the presence of a bacterial biofilm coating affects attachment characteristics. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: Attachment to the silicone hydrogel lenses was compared with that to a conventional hydrogel control lens. Sixteen replicates (n = 16) were carried out for unworn, worn, and biofilm-coated lenses of each type. METHODS: Unworn, worn, and Pseudomonas aeruginosa biofilm-coated first-generation (lotrafilcon A) and second-generation (galyfilcon A) silicone hydrogel and conventional hydrogel (etafilcon A) lens quarters were incubated for 90 minutes in suspensions of plate-cultured Acanthamoeba castellanii trophozoites. MAIN OUTCOME MEASURES: Trophozoites attached to one surface of each lens quarter were counted by direct light microscopy. Logarithmic transformation of data allowed the use of parametric analysis of variance for statistical analysis. RESULTS: Attachment of Acanthamoeba was affected significantly by lens material type (P<0.001), with higher numbers of trophozoites attaching to the first-generation lotrafilcon A silicone hydrogel lens, compared with the second-generation galyfilcon A lens and the conventional hydrogel lens. Attachments to the latter 2 lenses did not differ significantly from each other (P = 0.126). Patient wear and the presence of a bacterial biofilm had no significant effect on attachment to the lotrafilcon A lens (P = 0.426) but did significantly increase attachment to the galyfilcon A (P<0.001) and the etafilcon A (P = 0.009) lenses; attachment to the latter 2 lenses was still significantly less than that found with the first-generation silicone hydrogel (P<0.001). CONCLUSIONS: Acanthamoeba demonstrated a significantly greater affinity for the first-generation silicone hydrogel lens as compared with the second-generation silicone hydrogel and the conventional hydrogel. If exposed to Acanthamoeba (e.g., when showering or swimming, through noncontinuous wear and ineffective lens care regimes), first-generation silicone hydrogel lenses may promote a greater risk of Acanthamoeba infection due to the enhanced attachment characteristics of this lens material. However, prospective studies in patients are required to determine if these experimental results are clinically significant.
Leizaola-Fernández C, Suárez-Tatá L, Quiroz-Mercado H
… +5 more, Colina-Luquez J, Fromow-Guerra J, Jiménez-Sierra JM, Guerrero-Naranjo JL, Morales-Cantón V
BMC Ophthalmol
· 2005 May · PMID 15943889
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BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular disorder with potentially complications: (1) persistent macular edema and (2) neovascular glaucoma. No safe treatment exists that promotes th...BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular disorder with potentially complications: (1) persistent macular edema and (2) neovascular glaucoma. No safe treatment exists that promotes the return of lost vision. Eyes with CRVO may be predisposed to vitreous degeneration. It has been suggested that if the vitreous remains attached to the macula owing to a firm vitreomacular adhesion, the resultant vitreous traction can cause inflammation with retinal capillary dilation, leakage and subsequent edema6. The roll of vitrectomy in ischemic CRVO surgical procedures has not been evaluated. CASE PRESENTATION: This is a non comparative, prospective, longitudinal, experimental and descriptive series of cases. Ten eyes with ischemic CRVO. Vitrectomy with complete posterior hyaloid removal was performed. VA, rubeosis, intraocular pressure (IOP), and macular edema were evaluated clinically. Multifocal ERG (m-ERG), fluorescein angiography (FAG) and optic coherence tomography (OCT) were performed. Follow-up was at least 6 months. Moderate improvement of visual acuity was observed in 60% eyes and stabilized in 40%. IOP changed from 15.7 +/- 3.05 mmHg to 14.9 +/- 2.69 mmHg post-operative and macular edema from 976 +/- 196 microm to 640 +/- 191 microm to six month. The P1 wave amplitude changed from 25.46 +/- 12.4 mV to 20.54 +/- 11.2 mV. CONCLUSION: A solo PPV with posterior hyaloid removal may help to improve anatomic and functional retina conditions in some cases. These results should be considered when analyzing other surgical maneuvers.
Van Quill KR, Dioguardi PK, Tong CT
… +5 more, Gilbert JA, Aaberg TM, Grossniklaus HE, Edelhauser HF, O'Brien JM
Ophthalmology
· 2005 Jun · PMID 15885791
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PURPOSE: To evaluate the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma. DESIGN: Experimental study using LHbeta-Tag transgenic mice in a randomized control...PURPOSE: To evaluate the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma. DESIGN: Experimental study using LHbeta-Tag transgenic mice in a randomized controlled trial. PARTICIPANTS AND CONTROLS: Thirty-three 10-week-old LHbeta-Tag transgenic mice: 22 carboplatin-treated animals and 11 control animals. METHODS: Three groups of 11 mice were treated with a single, 30 microl injection of fibrin sealant in the subconjunctival space of 1 eye; the opposite eye was left untreated as an internal control. Group 1 (low-dose group) received 37.5 mg/ml calculated concentration of carboplatin in fibrin sealant (0.66 mg measured total dose). Group 2 (high-dose group) received 75 mg/ml calculated concentration of carboplatin in fibrin sealant (1.23 mg measured total dose). Group 3 (control group) received fibrin sealant only. Mice were killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis. For statistical analysis of treatment effects, eyes were divided into 6 groups: low-dose group, sealant-treated eyes; low-dose group, untreated eyes; high-dose group, sealant-treated eyes; high-dose group, untreated eyes; control group, sealant-treated eyes; and control group, untreated eyes. MAIN OUTCOME MEASURES: Main outcome measure was mean tumor burden per level per eye in each experimental group. RESULTS: The best therapeutic results were obtained in eyes treated with low-dose carboplatin in fibrin sealant, where no histopathologic evidence of toxicity was observed, and 6 of 11 eyes had zero tumor burden. Tumor burden in the remaining 5 eyes in this group was minimal (4 eyes) or moderate (1 eye) compared with mean control values. Mean tumor burden in this group was significantly smaller than mean tumor burden in untreated eyes from the same mice (P<0.004), sealant-treated eyes in the control group (P<0.004), and untreated eyes in the control group (P<0.002). Although a similar reduction in mean tumor burden was observed in eyes treated with high-dose carboplatin in fibrin sealant, 5 of 10 eyes analyzed in this group also demonstrated histopathologic evidence of severe toxicity. CONCLUSIONS: Subconjunctival carboplatin in fibrin sealant is effective in the treatment of transgenic murine retinoblastoma. A single injection of low-dose carboplatin in fibrin sealant was sufficient to induce complete or near-complete intraocular tumor regression in 10 of 11 eyes (91%), with no associated histologic evidence of toxicity. These results suggest that subconjunctival carboplatin in fibrin sealant provides sustained release and could have clinical use in the treatment of intraocular retinoblastoma.
Aldave AJ, Rayner SA, King JA
… +2 more, Affeldt JA, Yellore VS
Ophthalmology
· 2005 Jun · PMID 15885785
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PURPOSE: To report a unique corneal dystrophy characterized by deposits at Bowman's layer and stromal lattice lines associated with the Gly623Asp missense mutation in the transforming growth factor beta-induced (TGFBI) g...PURPOSE: To report a unique corneal dystrophy characterized by deposits at Bowman's layer and stromal lattice lines associated with the Gly623Asp missense mutation in the transforming growth factor beta-induced (TGFBI) gene. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: The proband, 3 affected siblings, 4 unaffected relatives, and 100 control individuals. METHODS: Slit-lamp examination, photographic documentation, and isolation of genomic DNA from buccal mucosal swabs obtained from each family member examined. Exons 4 and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members and in control individuals. MAIN OUTCOME MEASURES: Clinical characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene. RESULTS: Significant phenotypic variability, including polymorphic Bowman's layer opacities and stromal lattice lines, was noted in the 4 affected siblings who were examined. Screening of TGFBI exon 14 in the proband, 3 affected siblings, and a 19-year-old unaffected relative revealed a missense change, Gly623Asp, that was absent in the other 3 unaffected relatives screened and in 200 control chromosomes. CONCLUSIONS: We report a novel corneal dystrophy phenotype secondary to the Gly623Asp mutation in the TGFBI gene that is associated with clinical features of both lattice corneal dystrophy and a Bowman's layer dystrophy. The presence of clinical features considered atypical for a TGFBI-associated dystrophy in this pedigree, as well as the wide range of phenotypic expressions of the Gly623Asp mutation in affected members, underscore the clinical utility of molecular genetic analysis in the diagnosis of suspected corneal dystrophies.
Bellmann C, Feely M, Crossland MD
… +2 more, Kabanarou SA, Rubin GS
Ophthalmology
· 2004 Dec · PMID 15582084
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PURPOSE: To determine fixation stability for central and pericentral fixation targets in patients with age-related macular degeneration (AMD). DESIGN: Comparative study. PARTICIPANTS: Twelve patients having late-stage AM...PURPOSE: To determine fixation stability for central and pericentral fixation targets in patients with age-related macular degeneration (AMD). DESIGN: Comparative study. PARTICIPANTS: Twelve patients having late-stage AMD involving the fovea and 10 age-matched controls having no other eye diseases and visual acuity better than 20/25. METHODS: Six different fixation targets (1 degrees cross; 1 degrees filled circle; 1 degrees letter x; small 4-point diamond; large 4-point diamond using dimensions as in a field analyzer; large-crossover whole-image diagonal with open 1 degrees center) were presented on a high-resolution monitor. Before examination, subjects were given verbal instructions to move their eye to see the center of the target best. Fixation stability was measured for the preferred eye, with the fellow eye occluded, using a gaze tracker. Fixation stability was quantified by calculating the bivariate contour ellipse area (BCEA) over 30 seconds for each target. For statistical analysis, BCEA values (minutes of arc2) were converted into their logarithms. The absolute retinal scotoma for the study eye was determined using a scanning laser ophthalmoscope. MAIN OUTCOME MEASURE: Bivariate contour ellipse area. RESULTS: Visual acuity in patients (age range, 57-87 years) ranged from 20/32 to 20/600. The lowest BCEA values were found for the 1 degrees letter x in patients (mean, 12052.2%+/-254.0%) and for the 1 degrees cross in normal subjects (mean, 1286.9%+/-47.8%); the highest BCEA values were found for the small 4-point diamond in patients (mean, 23109.5%+/-298.3%) and for the large 4-point diamond in normals (age range, 62-79 years) (mean, 3229.2%+/-105.4%). The difference between the targets was significant for normal subjects (analysis of variance [ANOVA], P<0.01) but not for patients (ANOVA, P>0.05). In normals, BCEA values were significantly lower for central fixation targets than for pericentral fixation targets (P<0.01). CONCLUSION: Fixation is significantly less stable for pericentral fixation targets in normal subjects, indicating an advantage for central fixation targets. These results are particularly significant for any clinical and experimental testing method that requires the patient to maintain stable fixation.
OBJECTIVE: To develop a new technique to visualize vitreous body prolapsed in the anterior chamber using 11-deoxycortisol. STUDY DESIGN: Experimental study. METHODS: An animal model of posterior capsule rupture was devel...OBJECTIVE: To develop a new technique to visualize vitreous body prolapsed in the anterior chamber using 11-deoxycortisol. STUDY DESIGN: Experimental study. METHODS: An animal model of posterior capsule rupture was developed to investigate the usefulness of 11-deoxycortisol, a precursor of cortisol without steroid activity. After the intentional creation of posterior capsule rupture, the suspension of 11-deoxycortisol was injected into the anterior chamber of rabbit eyes. After gentle irrigation and aspiration, the vitreous body that had prolapsed into the anterior chamber was removed using an anterior vitrectomy cutter. To investigate the safety of 11-deoxycortisol, the biomicroscopic appearance, intraocular pressure (IOP), corneal endothelial count, and microstructure of the corneal endothelium were examined in the rabbits that received injections of 11-deoxycortisol in the anterior chamber. RESULTS: In our posterior capsule rupture model, the vitreous in the anterior chamber became clearly visible, with 11-deoxycortisol showing white particles entrapped on its surface. The injection of 11-deoxycortisol facilitated the complete removal of the vitreous body from the anterior chamber. In intact rabbit eyes, most of the injected 11-deoxycortisol had disappeared from the anterior chamber by 12 hours after injection. The injection of 11-deoxycortisol had no effect on IOP, corneal endothelial density, or the microstructure of the corneal endothelium. CONCLUSIONS: The injection of 11-deoxycortisol in the anterior chamber is useful in visualizing the vitreous body and has no significant side effects. This technique might reduce the intraoperative and postoperative complications of anterior vitrectomy after posterior capsule rupture.
Alvarez TL, Gollance SA, Thomas GA
… +8 more, Greene RJ, Marchetto PM, Moore EJ, Realini T, Liebmann JM, Ritch R, Lama P, Fechtner RD
Ophthalmology
· 2004 Jun · PMID 15177956
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PURPOSE: To evaluate the Proview Eye Pressure Monitor as a medical instrument and as a technique for enabling a patient to obtain an accurate measure of his or her intraocular pressure (IOP). DESIGN: An experimental labo...PURPOSE: To evaluate the Proview Eye Pressure Monitor as a medical instrument and as a technique for enabling a patient to obtain an accurate measure of his or her intraocular pressure (IOP). DESIGN: An experimental laboratory evaluation and an independent prospective clinical study to test the reproducibility and accuracy of the Proview technique relative to Goldmann applanation tonometry. PARTICIPANTS: For the laboratory study, we analyzed 3 tonometers, each packaged as a Proview Eye Pressure Monitor by Bausch & Lomb. In the independent prospective experimental study, 137 subjects participated, consisting of healthy volunteers and glaucoma patients. METHODS: For laboratory testing, we held each tonometer with a micrometer to assure controlled positioning and pressed its sensing tip against a force meter that produced a calibrated, digital force reading. For clinical testing, we taught subjects (n = 137) to use the Proview technique in accordance with the manufacturer's instructions. Each subject obtained 5 measurements with each of the 5 different Proview devices. A clinician measured the IOP using Goldmann applanation tonometry. MAIN OUTCOME MEASURES: We measured the absolute value, linearity, and repeatability of the force meter readings on the tonometers during the instrument laboratory evaluation. The accuracy was evaluated by comparing the Proview measurements to the Goldmann applanation measurements. Reproducibility of clinical Proview measurements was also measured. All measurements were in mmHg during the clinical evaluation. RESULTS: Laboratory: There was a linear relationship between the pressures read by the Proview tonometers and known forces. The Proview tonometers read the maximum pressure applied. Clinical: The Proview technique is simple to use because it was comfortable and reproducible, with an average variance of the measurements by the same patient of 3.4 mmHg(2). Other variables besides IOP seem to affect the Proview pressure measurements, as seen in the large scatter in our data, measured by our correlation coefficient of r = 0.41. The sensitivity of the Proview technique to detect patients with high IOP (which we defined as a Goldmann pressure of >/=22 mmHg) is low; the Proview pressure identified only 18% (4/22) of these patients. CONCLUSIONS: The Proview instrument and technique were reproducible. However, the Proview tonometer seems not to be reliable as an indicator of IOP. The sensitivity for detecting high IOP was low in this cohort, and the agreement with Goldmann applanation was poor for some individuals. This brings into question the underlying assumption that a force proportional to the IOP generates phosphenes.
Ophthalmology
· 2004 May · PMID 15121385
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PURPOSE: To outline the clinical features and surgical treatment of patients with familial and sporadic (simplex) forms of congenital fibrosis of extraocular muscles (CFEOM) from 2 countries, and to classify them accordi...PURPOSE: To outline the clinical features and surgical treatment of patients with familial and sporadic (simplex) forms of congenital fibrosis of extraocular muscles (CFEOM) from 2 countries, and to classify them according to phenotype and mode of inheritance. DESIGN: Observational and experimental study. METHODS: Twenty-eight affected individuals from 20 families with familial or sporadic CFEOM underwent assessment of ocular motility, visual acuity, slit-lamp biomicroscopy, tonometry, and ophthalmoscopy. Seventeen patients had a variety of eye muscle procedures and ptosis repair. RESULTS: There were 1 Iranian family with autosomal dominant CFEOM, 4 Iranian families with autosomal recessive disease, and 15 simplex cases with various CFEOM phenotypes. Two simplex patients had unilateral disease. All other cases were bilateral. Inferior rectus recession improved hypotropia and Bell's phenomenon in the patients with infraducted eyes and chin elevation. Horizontal muscle recession, sometimes combined with opposite muscle resection, corrected horizontal strabismus satisfactorily in most cases. Ptosis was repaired by frontalis sling and/or levator resection. CONCLUSION: Definite recessive CFEOM was present only in Iranian patients. American patients had the classic phenotype of dominant CFEOM, which was also observed in some of the Iranian patients. The surgical management of patients with CFEOM is challenging. Correction of vertical and horizontal strabismus was addressed using large muscle recessions. Ptosis repair should aim at placing the lid level 1 to 2 mm above the pupil in the primary position to avoid exposure keratopathy.
Wolf S, Schnurbusch U, Wiedemann P
… +3 more, Grosche J, Reichenbach A, Wolburg H
Ophthalmology
· 2004 Feb · PMID 15019369
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PURPOSE: To study the effects of internal limiting membrane (ILM) peeling, usually performed in cases of macular hole formation, on the structural integrity of the human retina. DESIGN: Experimental study. MATERIAL: Two...PURPOSE: To study the effects of internal limiting membrane (ILM) peeling, usually performed in cases of macular hole formation, on the structural integrity of the human retina. DESIGN: Experimental study. MATERIAL: Two human donor eyes. METHODS: A human donor retina was subjected to ILM peeling shortly after enucleation, fixed, and studied by electron microscopy. MAIN OUTCOME MEASURES: Electron microscopic findings. RESULTS: Within the peeled area, and even at its margins, a substantial number of Müller (glial) cell endfeet and vitreal Müller cell processes was severely damaged. However, many glial cells remained intact, and the cell bodies of the injured cells showed no signs of destruction. CONCLUSIONS: We have shown that ILM peeling results in minor, but demonstrable, damage of the adjacent retina. Clinical studies are required to demonstrate unequivocally that ILM peeling does not induce functional deficits rather than improvement of visual function.
Reviglio VE, Hakim MA, Song JK
… +1 more, O'Brien TP
BMC Ophthalmol
· 2003 Oct · PMID 14529574
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BACKGROUND: Matrix metalloproteinases play an important role in extracellular matrix deposition and degradation. Based on previous clinical observations of corneal perforations during topical fluoroquinolone treatment, w...BACKGROUND: Matrix metalloproteinases play an important role in extracellular matrix deposition and degradation. Based on previous clinical observations of corneal perforations during topical fluoroquinolone treatment, we decided to evaluate the comparative effects of various fluoroquinolone eye drops on the expression of matrix metalloproteinases (MMPs) in cornea. METHODS: Eighty female Lewis rats were divided into two experimental groups: intact and wounded corneal epithelium. Uniform corneal epithelial defects were created in the right eye with application of 75% alcohol in the center of the tissue for 6 seconds. The treatment groups were tested as follows: 1) Tear drops: carboxymethylcellulose sodium 0.5 % (Refresh, Allergan); 2) Ciprofloxacin 0.3% (Ciloxan, Alcon); 3) Ofloxacin 0.3%(Ocuflox, Allergan); 4) Levofloxacin 0.5%(Quixin, Santen). Eye drops were administered 6 times a day for 48 hours. Rats were sacrificed at 48 hours. Immunohistochemical analysis and zymography were conducted using antibodies specific to MMPs-1, 2, 8 and 9. RESULTS: MMP-1, MMP-2, MMP-8 and MMP-9 expression were detected at 48 hrs in undebrided corneal epithelium groups treated with the topical fluoroquinolones. No statistical difference was observed in quantitative expression of MMPs among ciprofloxacin 0.3%, ofloxacin 0.3%, levofloxacin 0.5%. When the artificial tear group and the fluoroquinolone groups with corneal epithelial defect were compared, increased expression of MMPs was observed as a result of the wound healing process. However, the fluoroquinolone treated group exhibited high statistically significantly levels of MMPs expression. CONCLUSIONS: Our study provides preliminary evidence that topical application of fluoroquinolone drugs can induce the expression of MMP-1, MMP-2, MMP-8 and MMP-9 in the undebrided corneal epithelium compared to artificial tear eye drops.
PURPOSE: To determine the effectiveness of a vitamin D analog, 1alpha-hydroxyvitamin D(2) (1alpha-OH-D(2)), in inhibiting retinoblastoma in a transgenic retinoblastoma model (LHbeta-Tag mouse) and to evaluate its toxicit...PURPOSE: To determine the effectiveness of a vitamin D analog, 1alpha-hydroxyvitamin D(2) (1alpha-OH-D(2)), in inhibiting retinoblastoma in a transgenic retinoblastoma model (LHbeta-Tag mouse) and to evaluate its toxicity. DESIGN: Experimental study using an animal (LHbeta-Tag transgenic mouse) randomized (controlled) trial. PARTICIPANTS AND CONTROLS: Two hundred seventeen LHbeta-Tag transgene-positive 8- to 10-week-old mice total; 179 drug-treated animals, 38 control animals. METHODS: Mice were fed a vitamin D- and calcium-restricted diet and were randomized to treatment groups receiving control (vehicle), or 0.1, 0.3, 0.5, or 1.0 micro g/day of 1alpha-OH-D(2) via oral gavage 5 times weekly for 5 weeks. Body weight was measured at the start of treatment and twice weekly during treatment. Animals were euthanized on the last day of treatment. The eyes were enucleated, processed histologically, and serially sectioned. Representative sections from the superior, middle, and inferior regions of each globe were examined microscopically and tumor areas were measured using Optimas software. Serum was collected for serum calcium levels. Kidneys were removed for histologic processing and were analyzed microscopically for kidney calcification. MAIN OUTCOME MEASURES: Mean tumor area was measured to determine drug effectiveness. Toxicity was assessed by survival, weight loss over the treatment period, serum calcium, and kidney calcification. RESULTS: The mean tumor size in each 1alpha-OH-D(2) group was smaller than controls (all P values < 0.02): control, 90,248 micro m(2); 0.1 micro g, 31,545 micro m(2); 0.3 micro g, 16,750 micro m(2); 0.5 micro g, 30,245 micro m(2); and 1.0 micro g, 16,049 micro m(2). No dose-dependent response curve was evident. The survival percentage for each group was as follows: control, 97%; 0.1 micro g, 91%; 0.3 micro g, 88%; 0.5 micro g, 70%; and 1.0 micro g, 63%. Mortality was higher in the 0.5- micro g and 1.0- micro g doses (P values < 0.01) compared with other treatment groups and with the control group. Serum calcium levels were significant in all treatment groups compared with controls (all P values < 0.0001). CONCLUSIONS: In the LHbeta-Tag mouse, 1alpha-OH-D(2) inhibits retinoblastoma with no significant increase in mortality in lower doses (0.1-0.3 micro g). 1alpha-OH-D(2) has approval by the Food and Drug Administration as an investigative drug for cancer treatment, and has shown efficacy with low toxicity in adult cancer trials. 1alpha-OH-D(2) meets the criteria for human clinical trials.
Ophthalmology
· 2002 May · PMID 11986084
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PURPOSE: To quantify the effect of topical corticosteroids on bacterial keratitis. CLINICAL RELEVANCE: Bacterial keratitis is an economically important infection affecting 1 in 10,000 Americans annually. The predisposing...PURPOSE: To quantify the effect of topical corticosteroids on bacterial keratitis. CLINICAL RELEVANCE: Bacterial keratitis is an economically important infection affecting 1 in 10,000 Americans annually. The predisposing factors, prior ocular health, infecting microorganisms, inflammatory severity, and therapeutic choices can affect the course and outcome. Antibacterial treatment is often curative but does not guarantee good vision. Because many treated patients develop a sight-limiting corneal problem, antiinflammatory therapy has sometimes been recommended. LITERATURE REVIEWED: Publications from 1950 to 2000 that evaluated the effect of corticosteroids on bacterial keratitis in animal experiments, case reports and series, case-comparison and cohort studies, and clinical trials were systematically identified by electronic and manual search strategies. RESULTS: The use of a topical corticosteroid before the diagnosis of bacterial keratitis significantly predisposed to ulcerative keratitis in eyes with preexisting corneal disease (odds ratio [OR], 2.63; 95% confidence limits [CL], 1.41, 4.91). Once microbial keratitis occurred, prior corticosteroid use significantly increased the odds of antibiotic treatment failure or other infectious complications (OR, 3.75; 95% CL, 2.52, 5.58). However, the effect of a topical corticosteroid with antibiotics after the onset of bacterial keratitis was unclear. Experimental models suggested likely advantages, but clinical studies did not show a significant effect of topical corticosteroid therapy on the outcome of bacterial keratitis (OR, 0.62; 95% CL, 0.25, 1.54). CONCLUSIONS: Topical corticosteroids increase the risk of infectious complications affecting the cornea but may or may not have an effect during antibacterial therapy. The unproven role of corticosteroids in the adjunctive treatment of bacterial keratitis highlights the need to collect prospective information that would guide appropriate management for this common eye disease.
OBJECTIVE: To study possible initial mechanisms of alterations in aqueous outflow that may result from the injection of viscoelastic into Schlemm's canal (SC) during viscocanalostomy. DESIGN: Experimental animal (Macaca...OBJECTIVE: To study possible initial mechanisms of alterations in aqueous outflow that may result from the injection of viscoelastic into Schlemm's canal (SC) during viscocanalostomy. DESIGN: Experimental animal (Macaca nemestrina) and human autopsy study. METHODS: Eyes were dissected into a limbal ring and hemisected or quartered. Uncannulated segments served as controls. In treated segments, SC was cannulated and viscoelastic injected. Segments were fixed and sectioned into continuous 500 to 1000 microm pieces, examined at the dissecting microscope, and photomicrographs were taken. Representative tissue was further prepared for scanning electron microscopy or sectioned at 1 microm. MAIN OUTCOME MEASURES: Tissue sections were examined to determine the extent of dilation and disruption of SC and related structures. SC dimensions were measured in segments from controls, cannulated regions, and regions of viscoelastic injection beyond the cannula insertion. In the hemisected segments, the circumferential extent of SC dilation was determined, and structures within the canal were described and counted. RESULTS: SC was dilated with increased anteroposterior length and height in cannulated and viscoelastic-injected segments in both primate and human eyes relative to untreated controls. The walls of SC were disrupted in both regions of cannulation and of viscoelastic injection, and the collector channels were widely dilated by viscoelastic. With decreasing effectiveness, the injected viscoelastic circumferentially dilated SC as far as 14 mm and 16 mm in primate and human hemisections, respectively. Structures that bridged between the walls of SC were often disrupted. CONCLUSIONS: Cannulation of SC and injection of viscoelastic beyond the cannula resulted in marked dilation of SC and associated collector channels. Lateral walls, inner wall endothelium, and bridging structures of SC were frequently disrupted by cannulation and sometimes by injected viscoelastic. These findings suggest that viscocanalostomy may acutely cause a direct communication between SC and the juxtacanalicular space, and so may initially enhance conventional aqueous outflow. Controlled clinical trials will be necessary to determine the long-term outcomes of this procedure.
Ophthalmology
· 2002 Mar · PMID 11874746
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PURPOSE: To develop a clinically specific strategy for optic nerve head (ONH) surface change detection within longitudinally acquired confocal scanning laser tomographic (CSLT) images. DESIGN: Experimental study. PARTICI...PURPOSE: To develop a clinically specific strategy for optic nerve head (ONH) surface change detection within longitudinally acquired confocal scanning laser tomographic (CSLT) images. DESIGN: Experimental study. PARTICIPANTS AND/OR CONTROLS: Twelve monkeys, each with one glaucomatous and one contralateral normal eye. MAIN OUTCOME MEASURES: Detection of ONH surface change within the CSLT images of each monkey's glaucomatous eye. METHODS: Six 10 and six 15 CSLT images and four stereo optic disc photographs were obtained from both eyes of 12 monkeys on 3 separate days (imaging sessions) and then every 2 weeks after laser to one eye (study eye) to elevate intraocular pressure. For each set of 10 and 15 images per eye (and for each of the 7-25 imaging sessions per monkey), 37 CSLT parameters were calculated. Univariate change required an individual parameter to change in excess of its analysis of variance-determined minimum detectable change (MDC) value. Multivariate change required groups of three parameters, considered together, to demonstrate significant change as determined by a multivariate analysis of variance. The rate of false-positive change detection for each individual parameter and for a group of three-parameter combinations was determined using both a one-in-a-row strategy (change at a single session) and a two-in-a-row strategy (change at two successive sessions) within the postlaser images of the 12 unchanging contralateral normal eyes. Change detection within the study eye images was then assessed for only those individual parameters and three-parameter combinations that were clinically specific (i.e., showed less than 10% false-positive change detection in the normal eyes). RESULTS: A total of 36 prelaser (three per monkey) imaging sessions and 158 postlaser (4-22/monkey) imaging sessions was performed. Clinically specific change detection (low rate of false positives) was achieved only with the two-in-a-row strategy. Overall, multivariate ONH surface change detection performed best; the best-performing three-parameter combination detected only 8 change events (4 onset and 4 progression) in 139 imaging sessions within the postlaser imaging sessions of the contralateral normal eyes and a total of 47 change events (11 onset and 36 progression) within the postlaser imaging sessions of the 12 study eyes. Counterintuitive (anterior) change occurred in most parameters within the late postlaser imaging sessions of the study eyes followed to end-stage damage. CONCLUSIONS: Clinically specific detection of the onset and progression of glaucomatous ONH surface change is possible within longitudinally acquired CSLT images.
Ophthalmology
· 2001 Nov · PMID 11713090
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PURPOSE: Loss of lens elasticity is one of several proposed mechanisms responsible for the decline in accommodation with age and is the most accepted explanation for presbyopia. We wish to confirm the lens elasticity pre...PURPOSE: Loss of lens elasticity is one of several proposed mechanisms responsible for the decline in accommodation with age and is the most accepted explanation for presbyopia. We wish to confirm the lens elasticity premise and attempt to experimentally reverse the age-dependent loss of accommodative potential as measured by polar strain. DESIGN: Experimental human autopsy eye study. PARTICIPANTS AND CONTROLS: Thirty-six cadaver lenses were tested to determine the age-dependent polar strain. Eleven lens pairs were then tested with one lens treated with neodymium:yttrium-aluminum-garnet (Nd:YAG) laser and the other left untreated before rotation as an age control. TESTING: Using a custom-made rotational apparatus (described by Fisher, 1971), freshly excised cadaver lenses (<48 hours postmortem) were rotated at 1000 rpm on a 9-mm diameter pedestal to simulate the physiologic pull of the zonules. Lenses were initially tested to determine the age-dependent polar strain. One lens in a pair was then treated with an Nd:YAG laser and the other left untreated before testing. Treatment consisted of 100 suprathreshold pulse placed in a central annular pattern of 2- to 4-mm diameter. Treatment energies varied from 2.5 to 7.0 mJ/pulse, depending on the relative clarity of the lenses. Polar strain was both microscopically measured and calculated from projected photographs before and after rotation of both lased and unlased lenses. Statistically significant differences were determined by paired t test. MAIN OUTCOME MEASURES: Polar strain (decrease in axial thickness with rotation) of the lens. RESULTS: An age-dependent decrease in polar strain was observed that paralleled the findings of Fisher. Both measured and projected polar strain were greater in the lased than unlased lens, and this difference was highly significant by paired t test (P = 0.001 and P = 0.004, respectively). CONCLUSIONS: Age-dependent loss of lens elasticity (polar strain) can be experimentally reversed (increased) by selective intralenticular photodisruption.
Ophthalmology
· 2001 Oct · PMID 11581043
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OBJECTIVE: To evaluate the safety and efficacy of laser in situ keratomileusis (LASIK) after removal of intrastromal corneal ring segments (Intacs, KeraVision, Fremont, CA) from the cornea. DESIGN: Single-center, noncomp...OBJECTIVE: To evaluate the safety and efficacy of laser in situ keratomileusis (LASIK) after removal of intrastromal corneal ring segments (Intacs, KeraVision, Fremont, CA) from the cornea. DESIGN: Single-center, noncomparative, interventional, consecutive case series. PARTICIPANTS: Nine eyes of nine consecutive patients who had undergone LASIK after Intacs of experimental design removal were analyzed for this study. INTERVENTION: A standard LASIK procedure was performed with the Nidek EC 5000 excimer laser (Nidek, Gamagori, Japan) at intervals between 4 and 10 months after Intacs explantation. A Nidek MK 2000 microkeratome (Nidek, Gamagori, Japan) or a Chiron Automated Corneal Shaper (Bausch & Lomb, Claremont, CA) with a 130- to 180-microm thickness plate was used to create a nasal hinged flap in a plane superficial to the previous Intacs channel. MAIN OUTCOME MEASURES: Uncorrected visual acuity, manifest refraction, best spectacle-corrected visual acuity, and topography were measured preoperatively and at months 1, 3, 6, and 12 after LASIK. RESULTS: Faint residual scarring in the channels after Intacs removal was seen in all patients. No difficulties were encountered during the ablation or flap replacement. Eight of nine patients had 20/20 or better uncorrected visual acuity after a single LASIK procedure. Mean spherical equivalent at 12 months was -0.6, ranging from -1.25 to +0.25 diopter. One patient had glare develop secondary to superior corneal thinning and scarring after implantation of a nonstandard Intacs. No patient lost lines of best spectacle-corrected vision after LASIK. CONCLUSION: Reversibility of the myopic Intacs is demonstrated. Removal of Intacs may be followed by a safe and effective LASIK for low to moderate myopia.
Krueger RR, Seiler T, Gruchman T
… +2 more, Mrochen M, Berlin MS
Ophthalmology
· 2001 Jun · PMID 11382631
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PURPOSE: To determine the stress wave amplitudes generated during photoablation of the cornea using an argon fluoride excimer laser. DESIGN: Experimental study using porcine eyes. METHODS: Profiles of the stress wave amp...PURPOSE: To determine the stress wave amplitudes generated during photoablation of the cornea using an argon fluoride excimer laser. DESIGN: Experimental study using porcine eyes. METHODS: Profiles of the stress wave amplitudes and enucleated human eyes along the axis of symmetry of porcine eyes and enucleated human eyes were measured using a miniature piezoelectric transducer. The ablation parameters, fluence, and ablation diameters were varied within the range of clinical application. MAIN OUTCOME MEASURES: Stress wave amplitudes generated during photoablation. RESULTS: The stress waves pass through a pressure focus located in the posterior lens and anterior vitreous, where amplitudes of up to 100 atm were measured with a 6-mm or larger ablation zone. Posterior to this focus, the stress wave amplitudes rapidly decrease to less than 10 atm at the retinal site. Small diameter excimer laser spots (< or =1.5 mm) produce a declining stress wave with no pressure focus at the lens and anterior vitreous. CONCLUSIONS: Stress waves may be potentially hazardous to anterior structures of the human eye, including the corneal endothelium, lens and anterior vitreous face. They peak at the lens and vitreous with a broad beam, but not with small spot laser ablation. At posterior retinal and subretinal structures, they may be considered harmless.
PURPOSE: A new form of aberrometry based on Tscherning optics has been proposed that captures the refraction and high-order aberrations of the eye with and without accommodation. DESIGN: Experimental clinical optics stud...PURPOSE: A new form of aberrometry based on Tscherning optics has been proposed that captures the refraction and high-order aberrations of the eye with and without accommodation. DESIGN: Experimental clinical optics study. METHOD: A green neodymium:yttrium-aluminum-garnet laser grid pattern is projected into the eye and viewed on the retina through a narrow, collimated aperture of 1 mm. The resulting aberrated pattern is photographically recorded in a normal eye in the unaccommodated and accommodated state through a pharmacologically dilated pupil without cycloplegia. MAIN OUTCOME MEASURES: Detection of pupil-dependent refraction and high-order optical aberration with and without accommodation. RESULTS: Subtle pupil-dependent errors in refraction and high-order aberrations (spherical aberrations and coma) are demonstrated in the unaccommodated normal eye. Accommodation reveals slightly more spherical power through the central 3-mm zone than through a 6.5-mm pupil without significant increase in aberration. CONCLUSIONS: Tscherning aberrometry based on 'retinal imaging' is useful in defining the refraction and optical aberrations in a normal eye. Accommodation increases spherical refractive power with only small aberration changes, including negative asphericity.
Miño De Kaspar H, Hoepfner AS, Engelbert M
… +10 more, Thiel M, Ta CN, Mette M, Schulze-Schwering M, Grasbon T, Sesma-Vea B, Casas JM, Iturralde-Goñi R, Klauss V, Kampik A
Ophthalmology
· 2001 Mar · PMID 11237900
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OBJECTIVE: To study whether the clinical outcome of Staphylococcus epidermidis-induced endophthalmitis in rabbits is related to the antibiotic resistance pattern of the infecting strain. DESIGN: Experimental animal study...OBJECTIVE: To study whether the clinical outcome of Staphylococcus epidermidis-induced endophthalmitis in rabbits is related to the antibiotic resistance pattern of the infecting strain. DESIGN: Experimental animal study. PARTICIPANTS: The right eyes of 36 New Zealand white albino rabbits were inoculated with strains of S. epidermidis that displayed various patterns of antibiotic resistance. METHODS: There were 12 rabbits in each of three study groups: fully antibiotic susceptible (FS), partially antibiotic resistant (PR), and multiresistant (MR). Five days after inoculation, the eyes were enucleated and prepared for histologic studies. MAIN OUTCOME MEASURES: Comparisons among the three groups were made based on electroretinographic (ERG) findings, histologic evaluation by a masked observer, and clinical examination. RESULTS: Electroretinographic findings on all rabbits were made by an unmasked observer. At 30 hours after inoculation, the ERG was diminished to 65% of normal for group FS, compared with a flat ERG waveform for groups PR (P < 0.05) and MR (P < 0.05). The ERG waveform was flat for all three groups at 72 hours after inoculation. Histologic evaluation by use of a histologic score revealed that the degree of inflammation and destruction of the retina was less for group FS (n = 10) compared with groups PR (n = 8) and MR (n = 8). Clinical examination revealed that there was a trend of less ocular inflammation for group FS compared with groups PR and MR. CONCLUSIONS: In a rabbit model of S. epidermidis-induced endophthalmitis, antibiotic-susceptible strains caused less inflammation and destruction of the infected retina than did antibiotic-resistant strains.