[Show abstract][Hide abstract] ABSTRACT: To evaluate the potential of topical iganidipine ophthalmic solution to exert Ca(2+)-antagonistic activity in the posterior parts of the eye without inducing systemic effects, ocular and periocular penetration of topically instilled iganidipine was studied in pigmented rabbits.
First, (14)C-iganidipine solution (0.03%, 30 microL) was instilled into one eye, and vehicle into the other eye to determine the intraocular penetration of iganidipine and to measure the radioactivity of ocular tissues 0.25, 0.5, 1, 2, 4, and 12 hours after a single instillation (n = 3, respectively). Second, iganidipine (0.03%) or betaxolol (0.5%) was unilaterally instilled twice daily for 20 days to study the effects on intravitreously injected various doses of endothelin (ET)-1-induced retinal artery constriction to evaluate whether a pharmacologically active level of the drug penetrated to the posterior retina and to estimate the drug level in the posterior retina (n = 6, respectively). Third, iganidipine (0, 10, or 30 microg/kg: n = 6, 3, and 6, respectively) was intravenously injected to study the effects on intravitreously injected ET-1-induced retinal artery constriction to evaluate iganidipine levels in the posterior retina. Fourth, periocular penetration of iganidipine was studied by means of whole-head autoradiography after a single instillation of (14)C-iganidipine (0.09%, 30 microL; n = 5).
Penetration of topically applied iganidipine to the cornea or aqueous humor was high and estimated to be at least 10 times higher than that reported for timolol or carteolol. Concentrations in the iris-ciliary body or retina-choroid were much higher than in the plasma, both in the treated and control eyes, suggesting that iganidipine binds to uveal pigments. Twice-daily 20-day instillation of iganidipine (0.03%), but not of betaxolol (0.5%), significantly suppressed constriction of the retinal arteries induced by intravitreous injection of ET-1 at a dose of 2.5 or 0.5 ng in the ipsilateral eye. Intravenous injection of iganidipine at a dose of 30 microg/kg (giving a free plasma concentration of approximately 10(-8) M), but not at a dose of 10 microg/kg, significantly suppressed intravitreous ET-1-induced (0.5 ng) constriction of the retinal artery to a similar degree as twice-daily 20-day instillation of 0.03% iganidipine. After a single instillation of 0.09% iganidipine, the equivalent concentration of iganidipine in the ipsilateral retrobulbar periocular space estimated from autoradiography was approximately 3.9 x 10(-8) M between 15 minutes and 1 hour after instillation, consistently higher than in the untreated contralateral eyes by approximately 3.0 x 10(-8) M (P = 0.043).
In rabbits, topically instilled iganidipine, a Ca(2+) antagonist, in a 0.03% solution reaches the ipsilateral posterior retina or retrobulbar periocular space by local penetration at concentrations sufficient to act as a Ca(2+) antagonist.
[Show abstract][Hide abstract] ABSTRACT: The corneal endothelium is a target of the aging process. This study was undertaken to reveal the relationship between corneal endothelial cell (CEC) death and the accumulation of advanced glycation end products (AGEs), by investigating the possible mechanism of accumulation of AGE in CECs and its effects on CEC death.
First, the in vivo expression of the receptor was investigated for AGE (RAGE) and galectin-3, both receptors for AGE, at both the mRNA and protein levels. Second, AGEs were added to the culture media of the cultured CECs, and the uptake of AGEs, the generation of reactive oxygen species, and the induction of apoptosis were investigated.
Immunohistochemistry and RT-PCR demonstrated that both RAGE and galectin-3 were expressed in bovine CECs. After administration of AGE-modified bovine serum albumin to the culture medium, uptake of AGE was observed in the cytoplasm of the cultured bovine CECs. In addition, with increasing concentration of AGEs, the generation of reactive oxygen and the number of apoptotic cells also increased.
These results show that the accumulation of AGEs in CECs induced apoptosis, in part, by increasing cellular oxidative stress. The accumulation of AGEs in the CECs of elderly patients may be involved in the loss of CECs during the aging process.
[Show abstract][Hide abstract] ABSTRACT: To describe the clinical characteristics of functioning blebs in Japanese glaucoma patients after primary trabeculectomy with adjunctive mitomycin-C (MMC) and to correlate their associations with postoperative bleb leakage.
A prospective, observational case series.
One hundred sixty-two glaucoma patients who had undergone primary trabeculectomy with MMC at the University of Tokyo Hospital at least 3 months before were examined between December 1997 and February 1998.
A predesigned data form was completed at each visit. Ophthalmologic examinations included Goldmann applanation tonometry, slit-lamp examination, and Seidel tests with and without digital ocular pressure (DOP).
Properties of the functioning bleb, including bleb appearance, thickness of bleb wall, dimensions of bleb and avascular area, and leakage status with and without DOP.
Of 162 Japanese patients, 162 eyes with functioning blebs were included. There were no differences in bleb characteristics among the different types of primary glaucoma. With a long postoperative duration, blebs tended to be thinner (P = 0.024). With DOP, the leaking rate increased from 3.1% to 5.6%, and the oozing rate increased from 11.1% to 35.8% (P < 0.001). Logistic regression analysis indicated that the larger the avascular area, the more likely the bleb leaked without DOP (P = 0.016). When DOP was applied, leakage was more likely to occur in the blebs with a long postoperative duration (P = 0.002) or with a large avascular area (P < 0.001).
The clinical characteristics of filtering blebs were similar in Japanese patients with different types of primary glaucoma. Blebs with a large avascular area were associated with a higher risk of bleb leakage. Attention to the increased chance of leakage induced by DOP is important, especially for blebs with a long postoperative duration. Ophthalmologists should be aware of late bleb-related complications in addition to bleb function.
[Show abstract][Hide abstract] ABSTRACT: We report 4 cases of complete posterior dislocation of an intraocular lens (IOL) in the capsular bag occurring a mean of 5.5 years after uneventful cataract surgery. In all 4 cases, posterior chamber IOLs were fixated within the capsulorhexis. The patients experienced sudden loss of vision without an episode of trauma or ocular disease. Using a 3-port pars plana vitrectomy, the IOLs were explanted through a limbal incision and a new IOL was sutured to the ciliary sulcus. Histological examination indicated that zonular fibers were severed at the site of insertion in the capsule.
Journal of Cataract and Refractive Surgery 10/2002; 28(9):1689-93. DOI:10.1016/S0886-3350(01)01178-6 · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the relationship between apparent accommodation in pseudophakic eyes, multifocal corneal effects, and wavefront aberrations of the cornea.
In 102 eyes of 86 patients who had undergone phacoemulsification and posterior chamber intraocular lens implantation, the amount of apparent accommodation was measured with an accommodometer. The degree of corneal multifocality was determined on the corneal topography by measuring the maximum and minimum corneal refractive powers within the pupillary area. Wavefront aberrations of the cornea were calculated by expanding the height data of the corneal topography into Zernike polynomials for individual pupil size. The influence of higher-order aberration on the retinal image quality was simulated by computing the point-spread function (PSF) and modulation-transfer function (MTF) from the aberration function.
There was a significant positive correlation between the amount of apparent accommodation and corneal multifocality (Pearson correlation coefficient, r = 0.451, P < 0.001). The coma-like aberration showed a significant positive correlation with the amount of apparent accommodation (r = 0.440, P < 0.001), but the spherical-like aberration did not (r = 0.001, P = 0.993). Among the coma-like aberrations, the component representing vertically asymmetrical distribution of corneal refractive power with greater refraction located in the lower part of the eye was most relevant to apparent accommodation. Computer simulation of PSF and MTF indicated that a focus shift of 0.5 D deteriorated the retinal image significantly more in eyes without higher-order aberrations than in eyes with a moderate amount of coma-like aberrations.
Coma-like aberration of the cornea, along with corneal multifocality, contributes to apparent accommodation in pseudophakic eyes.
[Show abstract][Hide abstract] ABSTRACT: To find the most appropriate color-coded scales for the anterior and posterior elevation maps of scanning slit topography in the screening of abnormal corneas such as keratoconus.
Retrospective case-control study.
Eighty eyes of 40 normal subjects and 175 eyes of 95 patients with keratoconus.
Anterior and posterior corneal elevations were assessed using Orbscan 2. Best-fit sphere maps were drawn with several color-coded scales: 2-, 5-, 10-, and 20-microm height per each color interval.
The maps were judged to be abnormal when more than three colors (discriminant number) were found within the central 3-mm area. For each color-coded scale, sensitivity, specificity, positive predictive value, negative predictive value, and sensitivity + specificity were calculated. After determining the most appropriate color-coded scales for the anterior and posterior elevation maps, validity of the discriminant number was assessed. By varying the discriminant number from two to eight, receiver operator characteristic (ROC) curves were created using the sensitivity and specificity for each threshold number.
The highest sensitivity + specificity values and highly balanced predictive values were obtained with the 10- and 20-microm scales for the anterior and posterior elevation maps, respectively. The ROC curve analyses showed that the best discriminant color number is three, indicating that maps with four or more colors within the central 3-mm area are judged abnormal in screening.
The 10- and 20-microm interval color scales are most appropriate for the anterior and posterior elevation maps of the scanning slit topography, respectively.
[Show abstract][Hide abstract] ABSTRACT: To assess the relation between magnitude of refractive correction and changes in higher order wavefront aberrations of the cornea after laser in situ keratomileusis.
Prospective, consecutive, nonrandomized comparative trial (self-controlled).
One hundred eyes of 53 patients with myopia (-2.0 to -13.0 diopters) were included.
Laser in situ keratomileusis was performed. Videokeratography measurements were conducted before and 1 month after surgery.
The videokeratography data were used to calculate the higher order wavefront aberrations of the cornea for both small (3 mm) and large (6 mm) pupils.
For a 3-mm pupil, the surgery significantly increased coma-like (2.4 +/- 1.3-fold, P < 0.001, paired t test) and spherical-like (1.8 +/- 0.9-fold, P < 0.001) aberrations. For a 6-mm pupil, both coma-like (4.4 +/- 3.3-fold, P < 0.001) and spherical-like (9.4 +/- 5.2-fold, P < 0.001) aberrations were significantly increased by surgery. The amount of achieved correction showed significant correlations with the changes in coma-like (Pearson correlation coefficient r = 0.446, P < 0.001) and spherical-like (r = 0.348, P < 0.001) aberrations for a 3-mm pupil, and coma-like (r = 0.566, P < 0.001) and spherical-like (r = 0.693, P < 0.001) aberrations for a 6-mm pupil. The eyes that lost 2 or more lines of baseline spectacle-corrected visual acuity showed significantly larger induced increases in coma-like (P = 0.003, Mann-Whitney U test) and spherical-like (P = 0.009) aberrations for a 3-mm pupil than those that either improved or remained within 1 line of spectacle-corrected visual acuity
Laser in situ keratomileusis, performed using the current algorithms, increases higher order wavefront aberrations of the cornea, dependent on the amount of refractive correction.
[Show abstract][Hide abstract] ABSTRACT: To evaluate quantitatively the influence of suture removal after penetrating keratoplasty on corneal refraction including irregular astigmatism.
Subjects were 42 eyes of 39 patients with clear corneal grafts who underwent suture removal after penetrating keratoplasty. Videokeratography data taken before and after suture removal were decomposed using Fourier harmonic analysis into spherical power, regular astigmatism, and irregular astigmatism (asymmetry and higher order irregularity).
On average, spherical power significantly increased after suture removal (p < 0.0001, paired t test), and regular astigmatism did not change significantly (p = 0.247). Suture removal significantly decreased asymmetry (p < 0.0001) and higher order irregularity (p < 0.0001).
Suture removal after penetrating keratoplasty induces myopic shift and reduction in irregular astigmatism of the cornea.
[Show abstract][Hide abstract] ABSTRACT: To easily perform reliable color Doppler imaging of the orbital vessels in seated subjects.
Experimental study. An apparatus mounting the color Doppler imaging probe through a spring plate on a slit-lamp system was devised. In 16 eyes of eight seated subjects, color Doppler imaging assessments of the central retinal artery using the apparatus and by the examiner's handheld manipulation were repeated with a 10-minute interval. The reproducibility coefficients were calculated regarding the color Doppler imaging indices, including peak systolic velocity, end diastolic velocity, and resistive index.
The color Doppler imaging indices obtained with the apparatus showed no significant differences from those obtained by handheld manipulation. The time required for each measurement using the apparatus was shorter than that by handheld manipulation, and reproducibility coefficients were significantly smaller by about 50%.
Color Doppler imaging can be easily performed with good reproducibility in seated subjects using this apparatus.
American Journal of Ophthalmology 03/2002; 133(2):270-2. DOI:10.1016/S0002-9394(01)01312-5 · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy of a new intraocular biodegradable polymer dexamethasone drug delivery system (DEX DDS) in a high-risk corneal transplantation model.
Lewis rats that received orthotopic corneal transplants (Balb/c mice donors) were divided into three groups (six rats in each); group 1 received no treatment and served as controls, group 2 was treated with 0.1% betamethasone eyedrops three times daily for 6 weeks, and group 3 received DEX DDS in the anterior chamber at the time of transplantation.
All grafts in the untreated control group were rejected within 8 days. In the betamethasone eyedrop group, five eyes (83%) were rejected during the 8-week study period. None of the grafts in the DEX DDS group was rejected. The administration of DEX DDS significantly prolonged the survival rate of the corneal grafts (p < 0.001, log-rank test).
DEX DDS is effective in suppressing graft rejection in high-risk corneal transplantation.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate the role of CD80 and CD86 costimulatory molecules in corneal allograft rejection. Anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) were administered after orthotopic corneal allograft transplantation. Graft rejection was observed by biomicroscopy. Population and localization of CD80(+)and CD86(+)cells in the cornea, cervical lymph nodes, and spleen were examined by flow cytometry and immunohistochemistry. The combined use of anti-CD80 and anti-CD86 mAbs was effective in prolonging corneal allograft survival. In the untreated mice bearing rejected graft, many CD86(+)and CD80(+)cells were found around the host-graft junctional area in the cornea, and CD86(high)cells were found in the cervical lymph node and spleen. In contrast, few CD86(+)or CD80(+)cells were observed in the cornea, cervical lymph node, and spleen from the mice treated with anti-CD80/CD86 mAbs. These results demonstrated a significant role of CD80 and CD86 costimulatory molecules in corneal allograft rejection.
Experimental Eye Research 02/2002; 74(1):131-9. DOI:10.1006/exer.2001.1109 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: [corrected] The purpose of this study was to evaluate the effect of advanced glycation end products (AGEs) in Descemet's membrane on the attachment and spreading of the corneal endothelial cells.
An anti-AGEs monoclonal antibody (6D12), which recognizes a N(epsilon)-carboxymethyl lysine (CML)-protein adduct as an epitope, was used for immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Fresh bovine Descemet's membrane was incubated for 4 weeks in the buffered solution with 500 mM of glucose-6-phosphate (G-6-P). In the incubated Descemet's membrane, the immunohistochemical localization of CML was examined. Type I collagen-, type IV collagen-, fibronectin-, or laminin-coated 96-well plates were glycated by G-6-P. The amount of CML was determined by ELISA using 6D12. Cultured bovine corneal endothelial cells were seeded onto glycated or non-glycated extracellular matrix (ECM) in 96-well plates and allowed to attach for 3 hours. The number and the surface area of the attached cells were examined.
Immunoreactivity to CML was detected in Descemet's membrane incubated in the buffered solution containing G-6-P. Glycation of fibronectin and laminin decreased the number and the surface area of the attached corneal endothelial cells. Aminoguanidine in the incubation mixture inhibited CML formation of ECM components and increased the number and the surface area of the attached corneal endothelial cells in a dose-dependent manner.
AGE formation on fibronectin and laminin attenuated the attachment and spreading of the corneal endothelial cells. AGEs' formation in Descemet's membrane may be responsible for the corneal endothelial cell loss with aging and corneal endothelial abnormalities in diabetic patients
Current Eye Research 01/2002; 23(6):469-77. DOI:10.1076/ceyr.23.6.469.6968 · 1.66 Impact Factor