[Show abstract][Hide abstract] ABSTRACT: Poor drug delivery to lesions in patients' eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood-retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases.
International Journal of Nanomedicine 02/2013; 8:495-504. DOI:10.2147/IJN.S30725 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims: It was the aim of this study to measure spectral transmission of the human crystalline lens in situ. Method: The crystalline lens was illuminated by one of four light-emitting diodes of different colors. The relative spectral transmittance of the human crystalline lens was measured with the Purkinje-Sanson mirror images over a wide range of ages. Result: The study evaluated 36 crystalline lenses of 28 subjects aged 21-76 years. There was a significant correlation between the age and spectral transmittance for blue light. Conclusion: Spectral transmittance of the crystalline lens in situ could be measured with Purkinje-Sanson mirror images.
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects of vitrectomy as a treatment for the proliferative diabetic retinopathy (PDR) in patients under 40 years old.
Sixty eyes of 37 patients under 40 years old with PDR who had undergone vitrectomy for the first time in Juntendo University Urayasu Hospital were included in this study. Preoperative condition, operation methods, visual acuity after operation and complications both during or after operation, especially neovascular glaucoma (NVG), were reviewed retrospectively.
Visual acuity improved in 43 eyes (72%) by more than 0.2 logMAR compared to that before the operation, remained stable in 4 eyes (6%) and deteriorated in 13 eyes (22%) by more than 0.2 logMAR compared to that before operation. Optic atrophy and phthisis caused by NVG constituted 69% of the causes of complicated final visual acuity. Male patients and patients who had both hypertension and proteinuria had significantly higher prevalence of NVG after vitrectomy (p < 0.05), and patients who retained their lens after the first vitrectomy had a significantly lower prevalence of NVG after the operation (p < 0.05).
In young PDR patients under 40 years old, postoperative NVG was the main reason for severe visual impairment. Multifactorial causes, both general and ophthalmic seem to be implicated in the onset and progression of NVG derived from PDR.
[Show abstract][Hide abstract] ABSTRACT: To clarify whether use of angiogenic vessel-homing peptide, Ala-Pro-Arg-Pro-Gly (APRPG)-modified liposomes encapsulating 3-([2,4-dimethylpyrrhol-5-yl] methylidenyl)-indolin-2-one (SU5416), an angiogenesis inhibitor, can inhibit the development of experimental choroidal neovascularization (CNV) in rats.
Liposomes were prepared using the thin-film hydration method. To set up the rat experimental CNV model, intense fundus laser photocoagulation at 6 spots per eye was performed on pigmented rats. After photocoagulation, the rats were divided into 4 groups (6 rats in each group): an APRPG-liposomal SU5416 treatment group and control groups treated with a balanced salt solution, APRPG liposomes, or soluble SU5416. Each rat received a single intravitreal injection immediately after the injury. One week or 2 weeks after laser injury, the extent of CNV was evaluated by perfusion with high-molecular-weight fluorescein isothiocyanate-dextran.
Two weeks after injection, the CNV area was significantly (P < .05) smaller in the APRPG-liposomal SU5416-treated group compared with the CNV area in the balanced salt solution-and APRPG liposome-treated groups.
Liposomes modified by APRPG and encapsulating SU5416 constitute a potential drug formulation for CNV treatment that would require only a single intravitreal injection.
This liposomal delivery may enable the sustained release of small molecules and be a new treatment modality for CNV.
Archives of ophthalmology 03/2011; 129(3):317-21. DOI:10.1001/archophthalmol.2011.12 · 4.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects of an intravitreal injection of autologous plasmin enzyme for macular edema associated with a branch retinal vein occlusion (BRVO).
Prospective, interventional case studies.
Twenty-six eyes of 26 patients (14 men and 12 women) with macular edema resulting from a BRVO were studied. None of the eyes had a posterior vitreous detachment (PVD). The average age at the onset of BRVO was 58.7 ± 6.6 years. The interval between onset of the macular edema and injection of autologous plasmin enzyme was 4.2 months. One international unit of autologous plasmin enzyme in 0.1 mL was injected into each vitreous. The presence of a PVD was evaluated 1 week after the injection, and the visual acuity and macular thickness were measured before and 1 week and 1, 3, 6, and 12 months after the autologous plasmin enzyme injection.
After the autologous plasmin enzyme injection, a total PVD was observed in 23 eyes and no PVD was observed in 3 eyes. The visual acuity gradually recovered after the injection, improved by 2 lines or more in 23 eyes, and remained unchanged in the 3 eyes. The retinal thickness also recovered gradually at 1, 3, 6, and 12 months. The mean retinal thickness was reduced from 602.12 to 253.62 μm at 12 months after surgery. It was reduced significantly after 1, 3, 6, and 12 months (P < .0001).
Intravitreal autologous plasmin enzyme may lead to an improvement of visual acuity and a reduction of macula edema in eyes with BRVO.
American Journal of Ophthalmology 12/2010; 150(6):876-82. DOI:10.1016/j.ajo.2010.06.005 · 3.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the effects of carbon beam irradiation with those of proton beam irradiation on the physiology of the retina of rats.
Eight-week-old Wister rats were used. The right eyes were irradiated with carbon beam (1, 2, 4, 8, and 16 Gy) or proton beam (4, 8, 16, and 24 Gy) with the rats under general anesthesia. Electroretinograms were recorded 1, 3, 6, and 12 months after the irradiation, and the amplitudes of the a and b waves were compared with those of control rats.
The amplitude of b waves was reduced more than that of a waves at lower irradiation doses with both types of irradiation. With carbon ion irradiation, the amplitudes of the b wave were significantly reduced after radiation doses of 8 and 16 Gy at 6 months and by radiation doses of 4, 8, and 16 Gy at 12 months. With proton beam irradiation, the b-wave amplitudes were significantly reduced after 16 and 24 Gy at 6 months and with doses of 8 Gy or greater at 12 months. For the maximum b-wave amplitude, a significant difference was observed in rats irradiated with carbon beams of 4 Gy or more and with proton beams of 8 Gy or more at 12 months after irradiation.
These results indicate that carbon beam irradiation is about two times more damaging than proton beam irradiation on the rat retina at the same dose.
International journal of radiation oncology, biology, physics 12/2010; 78(5):1532-40. DOI:10.1016/j.ijrobp.2010.07.003 · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Age-related macular degeneration (AMD) is a common cause of blindness in the elderly. Caucasian patients are predominantly affected by the dry form of AMD, whereas Japanese patients have predominantly the wet form of AMD and/or polypoidal choroidal vasculopathy (PCV). Although genetic association in the 10q26 (ARMS2/HTRA1) region has been established in many ethnic groups for dry-type AMD, typical wet-type AMD, and PCV, the contribution of the 1q32 (CFH) region seem to differ among these groups. Here we show a single nucleotide polymorphism (SNP) in the ARMS2/HTRA1 locus is associated in the whole genome for Japanese typical wet-type AMD (rs10490924: p = 4.1 x 10(-4), OR = 4.16) and PCV (rs10490924: p = 3.7 x 10(-8), OR = 2.72) followed by CFH (rs800292: p = 7.4 x 10(-5), OR = 2.08; p = 2.6 x 10(-4), OR = 2.00), which differs from previous studies in Caucasian populations. Moreover, a SNP (rs2241394) in complement component C3 gene showed significant association with PCV (p = 2.5 x 10(-3), OR = 3.47). We conclude that dry-type AMD, typical wet-type AMD, and PCV have both common and distinct genetic risks that become apparent when comparing Japanese versus Caucasian populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12177-009-9047-1) contains supplementary material, which is available to authorized users.
Journal of Ocular Biology Diseases and Informatics 12/2009; 2(4):164-175. DOI:10.1007/s12177-009-9047-1
[Show abstract][Hide abstract] ABSTRACT: We describe three eyes of two cases of severe degeneration of the macula following vitrectomy with indocyanine green-assisted internal limiting membrane peeling for idiopathic macular hole. We need to remember the possibility of these complications and have to select the procedures that are safest to use for macular hole surgery.
The Open Ophthalmology Journal 02/2008; 2(1):27-30. DOI:10.2174/1874364100802010027
[Show abstract][Hide abstract] ABSTRACT: The purpose of this article is to report the characteristics and advantages of using a newly designed quartz contact lens with slit illumination from an operating microscope for intraocular surgery. The new contact lens is made of quartz. The lens is convex-concave and is used in combination with slit illumination from an operating microscope. The optical properties of quartz make this lens less reflective with greater transmittance. The combination of a quartz contact lens with slit illumination provided a brighter and wider field of view than conventional lenses. This system enabled us to perform bimanual vitrectomy and scleral buckling surgery without indirect ophthalmoscope. Small intraocular structures in the posterior pole or in the periphery were detected more easily. In conclusion, the newly designed quartz lens with slit beam illumination from an operating microscope provided a bright, clear and wide surgical field, and allowed intraocular surgery to be performed more easily.
International Ophthalmology 01/2008; 29(3):169-71. DOI:10.1007/s10792-007-9181-3 · 0.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nocardia exalbida was first reported in 2006. We describe a first case of keratitis caused by Nocardia exalbida.
A patient presented after two weeks of unsuccessful treatment of a corneal ulcer in her right eye. Nocardia keratitis was diagnosed from her culture results, and the species Nocardia exalbida was determined by phylogenetic studies using gene sequence analysis of 16S RNA. The disk diffusion method showed that this Norcardia sp. was sensitive to many antibiotics. Initially, the patient was treated with topical and systemic antibiotics, and corneal epithelium quickly regenerated. But when corticosteroid eyedrops were added, there was a recurrence of the keratitis. Corticosteroids were stopped, and systemic trimethoprim-sulfamethoxazole and topical tobramycin, colistin, chloramphenicol and sulfisoxazole were given. Within one month the corneal ulcer and infiltration disappeared.
This is the first report of keratitis caused by Nocardia exalbida. This species is susceptible to many antibiotics in vitro and clinically. However, supplementation with corticosteroids can lead to recurrence, and care should be taken when corticosteroids are being considered.
International Ophthalmology 11/2007; 27(5):333-6. DOI:10.1007/s10792-007-9079-0 · 0.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The volume of the subretinal fluid can be used to assess the condition of different types of retinal and macular disorders. The purpose of this report is to introduce a method to measure the volume of the subretinal fluid with the images of the optical coherence tomography (OCT) Ophthalmoscope in three cases of central serous chorioretinopathy and one case of retinal pigment epithelial detachment. We used the topography-mode program of the OCT Ophthalmoscope and measured the average height of the retinal detachment. By multiplying the size of the area of the retinal detachment and the average height of the retinal detachment, the volume of subretinal fluid could be determined. Examples are given to show the results of volume measurement of subretinal fluid in cases of localized retinal detachments.
[Show abstract][Hide abstract] ABSTRACT: The effectiveness of vitreous surgery for diabetic macular edema (DME), and the correlation between the preoperative systemic and ocular conditions and the visual outcome following vitrectomy were studied. Visual acuity improved in about 50% of the eyes. Both visual acuity and foveal thickness recovered 12 months after surgery and the improvement of visual acuity occurred later than the recovery of foveal thickness. The preoperative systemic condition does not affect the improvement of visual acuity, and thus it is not necessary to wait for good diabetic control if surgery is indicated.
Annals of Ophthalmology 10/2007; 39(3):222-7. DOI:10.1007/s12009-007-0027-4 · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coagulation is the most serious complication of transpupillary thermotherapy(TTT) for choroidal neovascularization (CNV). To detect coagulation quickly, it is important to have good visibility of the fundus during exposure. With the existing laser optical system using a half mirror, the fundus image is dim, and coagulation is difficult to detect. We have improved the laser optical system for TTT. The purpose of this study was to improve the optical system and to estimate the usefulness of our new system compared with the current optical system.
We exchanged the half mirror used in the existing TTT optical system to a split mirror. The illumination intensities were measured and the visibility of fundus images were compared.
Illumination intensity was increased by means of the split mirror of the slit-lamp for the TTT laser optical system. The fundus image became brighter and clearer.
Improvement of the optical system was useful for safe and effective treatment of cases of CNV with an indication for TTT.
[Show abstract][Hide abstract] ABSTRACT: One of the unique features of the optical coherence tomography (OCT) ophthalmoscope is that it can record C scan images of the retina. The purpose of this study was to determine the best recording time to measure the retinal thickness with the OCT ophthalmoscope. In addition, the accuracy of the measurements was examined by comparing the values obtained by the OCT ophthalmoscope with those obtained with the Stratus OCT Model 3000 (OCT III) assuming that the OCT III gives an accurate measurement of retinal thickness.
The topography mode of the OCT ophthalmoscope was used. First, the average retinal thickness recorded with 2-s scans was compared with that recorded with 4-s scans for a recording area of 15 degreesx15 degrees. Next, the average retinal thickness recorded by the OCT ophthalmoscope was compared with that obtained by the Fast Macular Thickness program of the OCT III in patients with macular oedema.
The mean retinal thickness of the central area was 208.1 microm for both 2 and 4 s recording times. The average retinal thickness obtained by the OCT ophthalmoscope was highly correlated and not significantly different from the values obtained by the OCT III. The largest differences obtained by the two instruments were seen in the parts of the retina with accumulation of hard exudates.
Accurate measurements of retinal thickness can be obtained with the OCT ophthalmoscope by 2-s scans, and thus, the OCT ophthalmoscope can be a valuable instrument for clinical assessments of retinal thickness.
[Show abstract][Hide abstract] ABSTRACT: To study the effect of candidate single nucleotide polymorphisms (SNPs) on chromosome 10q26, recently shown to be associated with wet age-related macular degeneration (AMD) in Chinese and Caucasian cohorts, in a Japanese cohort.
Using genomic DNA isolated from peripheral blood of wet AMD cases and age-matched controls, we genotyped two SNPs, rs10490924, and rs11200638, on chromosome 10q26, 6.6 kb and 512 bp upstream of the HTRA1 gene, respectively, using temperature gradient capillary electrophoresis (TGCE) and direct sequencing. Association tests were performed for individual SNPs and jointly with SNP complement factor H (CFH) Y402H.
The two SNPs, rs10490924 and rs11200638, are in complete linkage disequilibrium (D'=1). Previous sequence comparisons among seventeen species revealed that the genomic region containing rs11200638 was highly conserved while the region surrounding rs10490924 was not. The allelic association test for rs11200638 yielded a p-value <10(-11). SNP rs11200638 conferred disease risk in an autosomal recessive fashion: Odds ratio was 10.1 (95% CI 4.36, 23.06), adjusted for SNP CFH 402, for those carrying two copies of the risk allele, whereas indistinguishable from unity if carrying only one risk allele.
The HTRA1 promoter polymorphism, rs11200638, is a strong candidate with a functional consequence that predisposes Japanese to develop neovascular AMD.
[Show abstract][Hide abstract] ABSTRACT: Pattern visual evoked potentials (pVEPs) were used to assess the visual function before, and 1 and 6 months after removal of an idiopathic epiretinal membrane (ERM) from eight eyes. All patients underwent a standard three-port pars plana vitrectomy to remove the ERM removal and cataract surgery. pVEPs were elicited by check sizes of 15', 30', 60', and 120' with a reversal rate of 2 reversals/s. One hundred responses were averaged with an analysis time of 300 ms. The amplitude ratio (affected eye/fellow eye) of the P100 component were significantly larger at 6 months with smaller check sizes, and the increase was accompanied by an improvement of the VA. The mean peak latency of P100 did not change significantly for all check sizes. We conclude that the improvement of the P100 amplitude with smaller check sizes resulted from the recovery of visual function after the ERM removal.