Tetsuo Tochikubo

Calcification of Hydroview H60M intraocular lenses: Aqueous humor analysis and comparisons with other intraocular lens materials

PURPOSE: To compare the level of calcification on Hydroview H60M hydrophilic acrylic intraocular lenses (IOLs) (Bausch & Lomb) and other IOL materials. SETTING: Omori Medical Center, Department of Ophthalmology, Toho University, Tokyo, Japan. METHODS: The levels of calcification on Hydroview H60M hydrophilic acrylic IOLs, AcrySof SA60AT hydrophobic acrylic IOLs (Alcon Surgical, Inc.), Sensar AR40e hydrophobic acrylic IOLs (Advanced Medical Optics), ClariFlex (Advanced Medical Optics) silicone IOLs, and the MeniFlex ENV13 (Menicon) poly(methyl methacrylate) IOLs were compared in a calcium phosphate solution containing albumin. In a concentration‐change experiment, the calcium and phosphate concentration levels were changed and the results observed by scanning electron microscopy. RESULTS: The Hydroview H60M IOL had the largest amount of deposits. Small amounts of deposits were found on the other IOLs in the following decreasing order: AcrySof SA60AT, Sensar AR40e, ClariFlex, and MeniFlex ENV13. The amount of deposits on the Hydroview H60M IOLs was statistically significantly greater than the amount on the other IOLs (P<.01). CONCLUSIONS: The hydrophilic acrylic IOLs (Hydroview H60M) had significantly higher amounts of calcified deposits than IOLs of other materials, indicating that hydrophilic acrylic IOLs easily accumulate calcified deposits in the body when the concentrations of calcium, phosphate, and albumin in the aqueous humor fluctuate as a result of a blood–aqueous barrier breakdown.

Biofilm formation on hydrophilic intraocular lens material

Purpose: To estimate bacterial biofilm formation on the hydrophilic acrylic (hydrogel) intraocular lens (IOL) Meridian (HP60M, Baush & Lomb) and to investigate a preventive effect against biofilm formation of hydrogel IOLs presoaked in antibiotics. Methods: Two Staphylococcus epidermidis strains, ATCC 12228 and ATCC 35984 (biofilm-producer), and an Enterococcus faecalis strain (KOS1, clinical isolate from an endophthalmitis patient) were used. Biofilms were cultivated on disks of different IOL materials: hydrogel, PMMA (polymethylmethacrylate), and acrylic. Biofilms were stained with crystal violet (CV), which served as an index of biofilm formation. The bacterial population was enumerated after biofilm homogenization. Biofilms were also examined by scanning electron microscopy (SEM). IOLs were presoaked in two antibiotics, levofloxacin (LVFX) and gatifloxacin (GFLX), and then the bacterial population was enumerated. As in vivo experiment, antibiotics-treated and nontreated Meridian IOLs were implanted in rabbit eyes, which served as an endophthalmitis model, and the bacterial population was enumerated. Results: The amount of biofilm formed was the least on hydrogel from among the three materials tested after 48- and 72-hr incubation (p < 0.05 to 0.01). The bacterial population was the least on hydrogel from among the three materials with ATCC 12228 (p < 0.05 to 0.01), and the bacterial population was significantly different between hydrogel and acrylic after 72-hr incubation with ATCC 35984 (p < 0.05). Biofilm by the two S. epidermidis strains were recognized after 24-hr incubation. Rates of biofilm-positive SEM fields, which were defined as being occupied by biofilm over at least half of the area, were increased through 72 hr with ATCC 35984. While the E. faecalis strain showed no bacterial adherence on the antibiotics-treated hydrogel IOLs, adherence of the S. epidermidis strain, ATCC 35984 was recognized on the LVFX-treated IOLs after 48-hr incubation (103 to 104 CFU/ml). In the rabbit in vivo model, the bacterial populations in eyes with an antibiotics-treated Meridian IOL were significantly smaller than in eyes with a nontreated IOL for 72 hr after surgery (p < 0.05 to 0.01). Conclusions: The biofilm formation was less on hydrogel than on other two materials tested. Hydrogel presoaked in antibiotics exhibited a preventive effect against biofilm formation at least for 24 hr in vitro and against bacterial proliferation in the rabbit in vivo endophthalmitis model.

Development and Efficacy of a Drug-Releasing Soft Contact Lens

PURPOSE The purpose of this study was to investigate the uptake and the release of antibiotics from a newly synthesized drug delivery hydrogel soft contact lens (SCL) using an ion ligand mechanism. METHODS The antibiotics used were Gatifloxacin (GFLX) and Moxifloxacin (MFLX). The uptake amount and the sustained-release kinetics of antibiotics were investigated in vitro, and were also compared with newly synthesized SCLs, etafilcon A and polymacon. The antibiotic concentrations in the cornea, aqueous humor, and crystalline lens, and the effect against bacterial proliferation were investigated in vivo using rabbit subjects. Additionally the drug release efficacy of the new SCL was compared with that of eye drop administrations. RESULTS In vitro, antibiotic uptake was increased with the weight percent (wt%) of the anionic group, and the released amount of antibiotics was highest during the initial 1 hour period, which then decreased over the next 72 hours. The released antibiotics volume of the new SCLs was significantly higher throughout 72 hours than that of the other two materials, etafilcon A and polymacon (P < 0.01). Whereas in vivo, the concentrations found in the cornea and aqueous humor were higher than those for the eye drop groups (P < 0.05 or P < 0.01). Antibiotic release at those sites decreased over 72 hours. No bacterial populations were detectable in the group treated with the new SCL presoaked in antibiotics throughout the experimental periods. CONCLUSIONS The new SCLs released the antibiotics over several days, and showed improved penetration into the eye, along with prevention of bacterial proliferation.

Evaluation of the Incidence of Endophthalmitis after Intravitreal Injection of Anti-Vascular Endothelial Growth Factor

Aims: To report the incidence of infectious and noninfectious endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor (VEGF) from a multicenter clinical trial in Japan. Methods: A retrospective multicenter review of the data of patients who received intravitreal anti-VEGF injections between January 2007 and March 2011 was undertaken. Cases with the clinical diagnosis of endophthalmitis resulting from intravitreal injection were identified and reviewed. Results: A total of 5,236 intravitreal anti-VEGF injections (1,209 intravitreal injections of bevacizumab, 3,827 injections of ranibizumab, and 200 injections of pegaptanib sodium) had been administered. Five patients (0.095%), all of whom had received bevacizumab, were diagnosed as having endophthalmitis after the intravitreal injection. All patients visited the institutes for re-examination within 1–2 days after the injection. Among the 5 patients, 2 (0.038%) were culture positive for Streptococcus oralis and Enterococcus faecalis, respectively. The remaining 3 eyes (0.057%) developed presumed noninfectious endophthalmitis. Conclusion: Although endophthalmitis is a rare complication associated with intravitreal injection, in this series intravitreal anti-VEGF injection caused infectious or noninfectious endophthalmitis at a relatively high frequency. Further investigations are needed to consider an appropriate injection protocol for minimizing the incidence rates of endophthalmitis, and to assess the optimal treatment protocol for intravitreal injection-related endophthalmitis although it was difficult to differentiate these two entities.

The Relationship between the Adhesion Characteristics of Acrylic Intraocular Lens Materials and Posterior Capsule Opacification

Purpose: To investigate the relationship between the adhesion characteristics of similarly designed hydrophobic acrylic intraocular lenses (IOLs) and posterior capsule opacification (PCO). Methods: Three similarly shaped hydrophobic acrylic IOLs with a sharp-edged optic were used. Adhesive force of IOLs was measured with a tackiness tester. Human lens epithelial cells (LECs) were grown on each IOL for 48 h. LECs were then stained with crystal violet, which served as an index of the amount of cells attached to IOLs. Cellular migration and proliferation assays were performed using chamber inserts containing a collagen membrane. After 96 h of incubation, the collagen membranes were stained with hematoxylin and eosin for analysis. Three similarly shaped IOLs were implanted in rabbits. The eyes were enucleated 3 weeks later and analyzed for PCO area. Results: Hydrophobic acrylic IOLs were classified into three groups: A (less adhesive), B (moderately) and C (highly). The migration area of LECs on the collagen membrane was 5.65 ± 4.5% in group A, 2.83 ± 2.1% in group B, and 1.41 ± 1.5% in group C, with a significant difference between groups A and C (p < 0.05). The mean percentage area of PCO in the rabbit eye was 19.4 ± 16.7% in group A, 17.5 ± 8.5% in group B, and 5.5 ± 3.8% in group C, with a significant difference between groups A and C (p < 0.05). Conclusion: Adhesive force of hydrophobic acrylic IOLs may play an important role in preventing PCO. Among the similarly shaped hydrophobic acrylic IOLs, IOLs of highly adhesive material inhibited LEC migration and PCO more than IOLs of less adhesive material.

Preventive Effect Against Post-Cataract Endophthalmitis: Drug Delivery Intraocular Lens versus Intracameral Antibiotics

Purpose: To compare hydrophilic acrylic intraocular lenses (IOLs) as an antibiotic drug-delivery system with intracameral antibiotic administration in terms of the ability to prevent endophthalmitis. Methods: Antibiotic solutions of 0.3% (3 mg/ml) and 0.5% (5 mg/ml) gatifloxacin (GFLX) and 0.5% (5 mg/ml) and 1.5% (15 mg/ml) levofloxacin (LVFX) were prepared. IOLs made of hydrophilic acrylic and silicone were used. Hydrophilic acrylic IOLs were allowed to adsorb the antibiotic solutions. A clinically isolated strain, KOS1, of Enterococcus faecalis was used to induce experimental endophthalmitis in vivo. Antibiotic concentrations were determined with high-performance liquid chromatography (HPLC). Twelve hydrophilic acrylic IOLs with antibiotics were used for the in vitro antibiotic concentration assay. In vivo experiments were conducted with 51 rabbits in total. Antibiotic concentrations in the aqueous humor and effects against bacterial proliferation were evaluated. Results: Concentrations of released antibiotics in vitro were highest on the first day and had decreased by the second day. When a comparison was made between similar initial concentrations, GFLX was released to a significantly higher concentration than LVFX (p < 0.001). In the antibiotic-treated IOL group, GFLX concentrations in the aqueous humor reached a peak at four hours postoperatively and then decreased. The intracameral antibiotic group showed similar tendencies, with a remarkably higher peak concentration. Effects against bacterial proliferation were comparable between the antibiotic-treated IOLs and intracameral antibiotic administration. Conclusions: Preventive effects against endophthalmitis were similar between antibiotic-treated IOL implantation and intracameral antibiotic administration.

Penetration of Levofloxacin into Human Aqueous Humor

This study was designed to measure the concentration of levofloxacin in aqueous humor after topical and oral administration in patients undergoing cataract extraction. Patients were randomly divided into four groups. Levofloxacin concentration in the aqueous humor was the highest in the group in which 600 mg was given orally plus five topical instillations before surgery. The aqueous humor levels of levofloxacin after topical and oral administration exceeded the minimum inhibitory concentrations for certain bacterial species that frequently cause intraocular infection.

Comparison of the influence of intracameral gentamicin, gatifloxacin, and moxifloxacin on the corneal endothelium in a rabbit model

PurposeTo compare the effect of three intracameral antibiotics, gentamicin (GM), gatifloxacin (GFLX), and moxifloxacin (MFLX), on the rabbit corneal endothelium.MethodsTwenty-four eyes from 18 rabbits were used. In the GM treatment group of 12 eyes, a dose of 20 mg/ml, 2 mg/ml, 200 μg/ml, or 20 μg/ml of GM was injected into the anterior chamber. In the GFLX and MFLX treatment groups were injected into the anterior chamber of three eyes. The central corneal thickness was measured. The eyes were then enucleated for observation under scanning electron microscopy.ResultsThree days after the intracameral injection, a significant difference in central corneal thickness was found between the GM 20 mg/ml group and the control group (P < 0.05), but not between any other groups. The damage rate at the endothelial cell level was 67% in the GM 20 mg/ml group, 56% in the GM 2 mg/ml group, 33% in the GM 200 μg/ml group, 22% in the GM 20 μg/ml group, 22% in the GFLX group, and 0% in the MFLX group.ConclusionsIntracameral GFLX or MFLX was almost nontoxic to the rabbit corneal endothelium, in contrast to the toxic results of intracameral GM 20 and 2 mg/ml.

Wegener Granulomatosis-associated Optic Perineuritis

Abstract Introdunction: We report two patients with optic perineuritis (OPN) and hypertrophic pachymeningitis in Wegener granulomatosis (WG). Case report: Patient 1: a 74-year-old man developed blurred vision in each eye, sequentially, over a year. In the first episode, visual acuity in the right eye was reduced to no light perception, and in the second episode, the vision in the left eye fell to 20/100. Brain and orbital magnetic resonance imaging (MRI) revealed abnormal enhancement in the meninges and the ipsilateral optic nerve sheath. T2-hyperintense lesions were found along the outer rim of the ipsilateral optic nerve. Seropositive proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA), microhematuria and multiple pulmonary nodules suggested the diagnosis of WG. Steroid therapy was initiated 3 months after the first onset, but with no clinical response. At the 2nd episode, rapid administration of steroid ameliorated visual disturbance and MRI lesions markedly. Patient 2: a 72-year-old man developed blurred vision in each eye. Visual acuity measured no light perception in OD and 6/12 in OS. Gadolinium-enhanced MRI disclosed enhancement in the meninges and both optic nerve sheaths. T2-weighted imaging displayed hyperintense lesions along the outer rims of optic nerves. Otolaryngologic examination, seropositive PR3-ANCA and pulmonary nodules supported the diagnosis of WG. Steroid and cyclophosphamide treatment improved visual dysfunction and MRI lesions in the meninges and the optic nerve sheaths. Comment: The morphological similarity and the anatomical continuity between the meningeal and the perioptic tissues suggest that extension of granulomatous inflammation along such tissue planes accounted for visual loss in these two patients with WG.

Calcification and Membrane Formation on the Surface of Intraocular Lenses in a Rabbit Model

Purpose: The aim of this study is to evaluate the calcification and membrane formation in different intraocular lenses (IOLs) models by implanting the IOLs in the subcutaneous plane of a Rabbit model. Design: Experimental study. Methods: IOLs were implanted subcutaneously in 13 Japanese albino rabbits for 1 month (n = 6), 3 months (n = 4) and 6 months (n = 3). Five kinds of IOLs were used, including three hydrophobic acrylic IOLs, the MA60AC (Alcon), ZA9003 (AMO) and X-60 (Santen), and two hydrophilic acrylic IOLs, the HP60M and MI60 (Bausch & Lomb). Scanning electron microscopy was used to observe the IOL optics. Energy dispersive x-ray spectroscopy and infrared spectroscopy were used to analyse any surface depositions on the optics, and the modulation transfer function was applied to evaluate the optical performance. Results: Membrane formation was noted to have occurred on the surfaces of the two hydrophobic acrylic IOLs (MA60AC and ZA9003) during the investigation period. The membrane components originated from a serum protein that most likely would be serum albumin. Calcification was noted to have occurred on the surfaces of the two hydrophilic IOLs. However, no calcification was observed on the hydrophobic IOLs, nor was there any membrane formation on the hydrophilic IOLs. The values for the MI60 were not measurable at all at 3 or 6 months. The values of the three hydrophobic IOLs were significantly better than the value for the HP60M at three and six months (p < 0.01). Conclusion: Calcification to the hydrophilic IOLs severely affected optical performance, whereas, membrane formation on the hydrophobic IOLs did not affect optical performance. The X-60 had the optics that best maintained long-term transparency.