Computer-assisted hydrodynamic gene delivery.

The recently developed hydrodynamic delivery method makes it possible to deliver DNA and RNA into parenchyma cells by intravascular injection of nucleic acid-containing solution. While this procedure is effective in rodents, it is difficult to perform in large animals, because manual control while delivering the injection cannot be sufficiently reliable for achieving a just-right hydrodynamic pressure in targeted tissue. In order to overcome this problem, we have developed a computer-controlled injection device that uses real-time intravascular pressure as a regulator. Using the new injection device, and mouse liver as the model organ, we demonstrated continuous injection at a single pressure and different pressures, and also serial (repeated) injections at intervals of 250 ms, by programming the computer according to the need. When assessed by reporter plasmids, the computer-controlled injection device exhibits gene delivery efficiency similar to that of conventional hydrodynamic injection. The device is also effective in gene delivery to kidney and muscle cells in rats, with plasmids or adenoviral vectors as gene carriers. Successful gene delivery to liver and kidney was also demonstrated in pigs, with the computer-controlled injection being combined with image-guided catheterization. These results represent a significant advance in in vivo gene delivery research, with potential for use in gene therapy in humans.

Midterm results and the problems of nonpenetrating lamellar trabeculectomy with mitomycin C for Japanese glaucoma patients.

PURPOSE: To present midterm results and problems pertaining to nonpenetrating lamellar trabeculectomy (NPT) with mitomycin C (MMC) for Japanese glaucoma patients. METHODS: Thirty-nine patients (39 eyes) with primary open-angle glaucoma or normal-tension glaucoma underwent NPT. The results were compared with those in patients treated by penetrating trabeculectomy (PT) with MMC. In addition, the NPT patients were classified into two groups (group A, 24 patients treated between April 1998 and April 1999; group B, 21 patients treated from May 1999 onward), and the results were compared. RESULTS: The average intraocular pressure (IOP) was 12.6 +/- 2.8 mmHg with NPT and 12.4 +/- 3.0 mmHg with PT. No statistical differences between NPT and PT were identified with respect to IOP at any time after surgery. A life-table analysis showed that the probability of success (good IOP control) was 37.2% with NPT and 62.5% with PT. No significant difference was detected in postoperative IOP change or in the probability of success between NPT groups A and B. CONCLUSIONS: While postoperative IOP is similar between PT and NPT, the probability of success is better with PT than with NPT. Postoperative laser treatment after NPT is effective but sometimes has a negative influence on IOP control.

Comparison of fornix- and limbus-based conjunctival flaps in mitomycin C trabeculectomy with laser suture lysis in Japanese glaucoma patients.

PURPOSE: To analyze the results of mitomycin C (MMC) trabeculectomy and laser suture lysis using either fornix-based (FB) or limbus-based (LB) conjunctival flaps. METHODS: Eighty-two Japanese glaucoma patients were treated by MMC trabeculectomy, with 38 eyes receiving an FB conjunctival flap and 44 eyes receiving an LB conjunctival flap. Postoperative intraocular pressure (IOP), the probability of success, and complications were compared between the FB and LB groups. RESULTS: The IOP of the FB group decreased from 21.6+/-7.90 mmHg to 9.75+/-3.23 mmHg at 12 months postoperation, and the IOP of the LB group decreased from 21.3+/-6.77 mmHg to 9.30+/-3.16 mmHg. The postoperative IOPs were similar in the two groups at all postoperative time points. A life-table analysis (Kaplan-Meier method) showed that the survival rate was similar in the two groups but tended to be lower in the early postoperative period in the FB group. Complications were similar also, with the exception of increased leakage in the FB group. CONCLUSIONS: MMC trabeculectomy results were similar between FB and LB conjunctival flaps, in agreement with previous reports. However, increased care may be warranted when an FB flap is used in MMC trabeculectomy.

The outcome of mitomycin C trabeculectomy and laser suture lysis depends on postoperative management.

PURPOSE: To verify that postoperative management affects the outcome of mitomycin C (MMC) trabeculectomy and suture lysis. METHODS: A total of 108 eyes in 108 Japanese patients were treated with MMC trabeculectomy. They were divided into two groups based on when the operation was performed: group A, 57 eyes in 1998, and group B, 51 eyes in 2001. The results, including postoperative intraocular pressure (IOP), complications, and postoperative management, were compared between groups. In addition, they were evaluated by a Kaplan-Meier life-table analysis. RESULTS: Postoperative IOP was lower and the probability of success by life-table analysis was higher in group B than in group A. Postoperative management, including laser suture lysis and subconjunctival injection of 5-fluorouracil, was started significantly earlier in group B than in group A patients. Although more postoperative complications occurred in group B, none were severe and all were adequately managed. CONCLUSIONS: Starting postoperative management earlier, particularly laser suture lysis, may be necessary to achieve lower and longer IOP control in MMC trabeculectomy.

[Two cases of Senior-Loken syndrome].

BACKGROUND: We report two rare cases of Senior-Loken syndrome, one with fundus lesions simulating Coats disease. CASE 1: A 14-year-old boy had juvenile nephronophthisis and bilateral retinitis pigmentosa with retionochoroidal atrophy and salt and pepper fundus. Electroretinogram (ERG) showed non-recordable changes and the Goldmann perimeter showed ring scotomas. CASE 2: A 14-year-old boy had bilateral retinitis pigmentosa and juvenile nephronophthisis with continuous ambulatory peritoneal dialysis. Additionally, both eyes showed massive exudates seen in Coats disease in the entire periphery, exudative retinal detachment, proliferative changes in the inferior periphery, yellow opacitas corporis vitrei, keratoconus, and cataract. The left eye had vitreous hemorrhages. Both eyes received vitreous surgery and endophotocoagulation. After the surgery the left eye showed neovascular glaucoma and a cyclophotcoagulation was performed. The massive edema in the superior retina of both eyes disappeared and intra-ocular pressure in the left eye was normalized. However, despite these treatments, both eyes finally had no light perception. CONCLUSION: Case 1 was a typical SLS, and case 2 was a rare one with fundus lesions simulating Coats disease, keratoconus, and cataract. We suspect the exudative changes resulted from various vessel changes and choroidal circulatory disturbance of renal retinopathy, retinal vascular damage, and destruction of blood-retinal barrier with retinitis pigmentosa, the inflammatory changes of vessels, and other things.

[A case of steroid-induced glaucoma after radial keratotomy].

BACKGROUND: We report a patient who was diagnosed as having steroid-induced glaucoma after radial keratotomy(RK) and suffered from severe visual field defect. CASE: A 29-year-old man underwent RK for both eyes. After the operation, he was treated for six months with topical medication including 0.1% and 0.01% betamethasone without measuring intraocular pressure(IOP). When he consulted an ophthalmologist, his IOP was 43 mmHg in the right eye and 51 mmHg in the left eye. At our initial examination, his IOP was 8 mmHg in the right eye and 10 mmHg in the left eye with 750 mg acetazolamide peroral, 0.5% timolol maleate, and latanoprost eyedrops. There were RK 16 incisions on the cornea and we found severe glaucomatous visual field loss. Finally we performed trabeculotomy in both eyes for IOP control with conservative therapy. CONCLUSION: As the keratorefractive surgery becomes popular, we must be careful of problems, such as steroid-induced glaucoma, and the change of refraction following the change of IOP.

[A case of acute angle-closure glaucoma secondary to annular ciliochoroidal detachment after unsutured cataract surgery].

BACKGROUND: We report a patient with acute angle-closure glaucoma secondary to annular ciliochoroidal detachment after unsutured cataract surgery. CASE: An 82-year-old man was diagnosed with bilateral shallow central anterior chamber depth, flat peripheral anterior chamber, and elevated intraocular pressure. One day previously he had undergone uncomplicated unsutured cataract surgery in the right eye and eight days previously, in the left eye. Ultrasound biomicroscopy revealed annular ciliochoroidal detachment in both eyes. Treatment with intravenous methyl prednisolone deepened the anterior chamber and reduced intraocular pressure. CONCLUSION: Annular ciliochoroidal detachment may lead to anterior rotation of the ciliary body and angle-closure. This clinical entity is indistinguishable from malignant glaucoma when the fundus cannot be visualized.

[Changes in filtering bleb with laser treatment after non-penetrating trabeculectomy].

PURPOSE: Ultrasound biomicroscopy(UBM) was performed on filtering blebs with laser treatment including laser gonioplasty(GP), laser iridotomy(LI), and YAG laser trabeculopuncture(YLT) after non-penetrating trabeculectomy(NPT). The filtering blebs were grouped into four types, L, H, E and F, and the spaces under the scleral flap were classified into three. La, S, and N. CASES: In case 1, an F type, an S bleb was not changed despite laser treatment 9 months after NPT. In case 2, YLT was performed twice to release the incarcerated iris. The filtering bleb was changed to the L type, an La bleb. In case 3, an F type, an S bleb was turned into an H type after GP, LI, and YLT. In case 4, GP effectively released peripheral anterior synechia formation and the filtering bleb was kept as an L type, La. CONCLUSION: Appropriate laser treatment may be effective in turning a flattened and localized bleb into a good filtering bleb.

Nanophthalmos: quantitative analysis of anterior chamber angle configuration before and after cataract surgery.

BACKGROUND/AIMS: To analyse quantitatively the anterior segment configuration in eyes with nanophthalmos before and after cataract surgery. METHODS: This was a retrospective, non-comparative, interventional case series. Eleven eyes in eight patients with nanophthalmos who underwent phacoemulsification and intraocular lens implantation were identified from the department's surgical log, and their clinical records were retrospectively reviewed. Main outcome measures were as follows: visual acuity, intraocular pressure (IOP), axial length and the following ultrasound biomicroscopy parameters: angle opening distance at 500 µm anterior to the scleral spur (AOD500), trabecular-iris angle (TIA) and trabecular ciliary process distance. RESULTS: The mean axial length of the eyes was 17.3 ± 1.7 mm. AOD500 and TIA increased after cataract surgery (p<0.005). Smaller axial length, AOD500 and TIA before cataract surgery were observed in eyes with preoperative IOP elevation than those without preoperative IOP elevation (p<0.05). Lower postoperative IOP was correlated with greater AOD500 and TIA before cataract surgery (p<0.05). CONCLUSIONS: Cataract surgery deepened the anterior chamber and widened the anterior chamber angle in nanophthalmic eyes. Cataract surgery may have beneficial effects on IOP in eyes with nanophthalmos.

Trabeculotomy combined with phacoemulsification, intraocular lens implantation and sinusotomy for exfoliation glaucoma.

PURPOSE: To verify the advantages of trabeculotomy combined with phacoemulsification, intraocular lens implantation and sinusotomy (PTOS) in eyes with exfoliation glaucoma (XFG) and a coexisting cataract. PATIENTS AND METHODS: Sixty-six eyes of 62 Japanese XFG patients that received either PTOS, phacotrabeculectomy (PTE) or MMC trabeculectomy (LEC) were followed for up to 36 months at Niigata University Medical and Dental Hospital. The outcomes of postoperative intraocular pressure (IOP) and visual acuity as well as complications were compared among the patients who underwent the three surgical procedures. RESULTS: The average preoperative IOP in the PTOS cases was 22.4 ± 5.13 mmHg, but decreased to 12.3 ± 2.33 mmHg at 12 months post-surgery and was maintained for up to 36 months. The preoperative IOPs, which were 21.9 ± 4.18 mmHg in the PTE group and 26.6 ± 7.57 mmHg in the LEC group, decreased to 13.3 ± 2.79 mmHg in the PTE group and 12.6 ± 6.00 mmHg in the LEC group at 12 months. There were no statistical differences among the three groups at any time point after 3 months. While the postoperative corrected visual acuities were similar between the PTOS and PTE groups, the average time in which the best postoperative visual acuity was reached was significantly shorter in the PTOS group (1.37 ± 1.74 months) than in the PTE group (4.92 ± 4.36 months). CONCLUSIONS: PTOS can be recommended as an initial glaucoma surgery for XFG eyes with coexisting cataracts, because PTOS is not a filtering surgery, but can obtain similar IOP effects as PTE for XFG eyes.

Corneal lamellar grafting to repair late complications of mitomycin C trabeculectomy.

PURPOSE: To report corneal lamellar grafting to repair the late-onset complications after MMC trabeculectomy. METHODS: Multiple case reports. RESULTS: A 76-year-old male with primary open-angle glaucoma (POAG) and a 55-year-old male with late developmental glaucoma complicated by bleb leaks from a microhole 10 and eight years after surgery, respectively. Severe ciliochoroidal detachment and a shallow anterior chamber were persistent in one case and bleb-related infection recurred in another. Additionally, a 46-year-old male with POAG had hypotony maculopathy with a giant ischemic bleb 18 months after surgery. Although these patients were quite resistant to medical and surgical treatments, they were successfully treated by corneal lamellar grafting without complications. CONCLUSIONS: Tectonic corneal lamellar grafting is a reliable and final surgical method to improve severe cases of hypotony maculopathy or bleb leak after mitomycin C trabeculectomy.

Incidence, severity and factors related to drug-induced keratoepitheliopathy with glaucoma medications.

PURPOSE: To evaluate the incidence, severity, and factors related to drug-induced keratoepitheliopathy in eyes using antiglaucoma eye drops. PATIENTS AND METHODS: In a cross-sectional study, 749 eyes from 427 patients who had used one or more antiglaucoma eye drops were examined at Niigata University Medical and Dental Hospital or related facilities. The incidence and severity of superficial punctate keratitis (SPK), patient gender and age, type of glaucoma, and type of eye drops were recorded. SPK was graded according to the AD (A, area; D, density) classification. The severity score (SS) was calculated from A x D. RESULTS: SPK was observed in 382 (51.0%) of 749 eyes that had received any type of antiglaucoma eye drops. While 254 eyes (33.9%) were classified as A1D1 (SS 1), 34 eyes (4.6%) had severe SPK with SS 4 or more. The number of eye drops and the total dosing frequency per day were significantly greater in SPK-positive eyes than in eyes without SPK. The number of eye drops was proportional to the frequency and severity of SPK. Among eyes that were treated with three or more eye drops, SPK was more severe and more frequent in older patients (>/=71 years). In addition, a considerable difference was detected for each type of glaucoma. CONCLUSION: Drug-induced keratoepitheliopathy is often observed in eyes that have received recent antiglaucoma eye drops. The number of eye drops, the total dose frequency per day, patient age, and type of glaucoma may affect this condition. We have to consider not only the effects on intraocular pressure but also the incidence and severity of drug-induced keratoepitheliopathy as a frequent side effect of glaucoma medications.