Toshiro Tanahashi

Does the enlargement of retinal nerve fiber layer defects relate to disc hemorrhage or progressive visual field loss in normal-tension glaucoma?

PurposeWe investigated the difference in clinical characteristics between cases with enlarged retinal nerve fiber layer defects (RNFLD) and stable RNFLDs in normal-tension glaucoma (NTG). Patients and MethodsWe retrospectively reviewed NTG patients that were diagnosed and followed up for at least 3 years at 1-month to 2-month intervals by the same examiner, and selected eyes with distinct RNFLD borders. Using fundus photographs, for which we extracted only a blue ingredient and processed it into black and white, we measured RNFLD angles and divided NTG cases into 2 groups, enlarged RNFLD and stable RNFLD, and compared the clinical characteristics between both groups. ResultsNinety-three eyes from 93 patients (mean follow-up, 8.2 y) were selected and enlargement of RNFLD was detected in 55 eyes. Disc hemorrhage (DH) was found in 35 of 55 eyes (63.6%) in the enlarged group and in 6 of 38 eyes (15.8%) in the stable group (P<0.0001). Twenty-one eyes (38.2%) from the enlarged group exhibited recurrent DH. In 48 eyes (87.3%) from the enlarged group, the enlargement of RNFLD was toward the fovea. When DHs located apart from RNFLD were excluded, RNFLD enlarged in the direction of DH in 21 of 25 eyes (84.0%). The cumulative probability of non progression in the visual field was significantly lower in the enlarged group (10–year survival rate: 0.52±0.11) than in the stable group (10-year survival rate: 0.89±0.08) (P=0.0019). ConclusionsThe enlargement of RNFLD in NTG was closely associated with DH occurrence and the deterioration of visual field.

Temporary use of a customized, glued-on hard contact lens before penetrating keratoplasty for descemetocele or corneal perforation

Descemetocele or corneal perforation makes it difficult to perform penetrating keratoplasty (PKP). To circumvent this difficulty, a polymethylmethacrylate hard contact lens with a diameter of 4.0 mm was customized and applied to the cornea with tissue adhesive prior to PKP in three patients, one with corneal perforation and two with descemetoceles. The results showed that this modified method facilitated trephination during PKP without complications in all three patients, suggesting that it may be applicable to other similar clinical situations.

Effects of norfloxacin on the retina in rabbits

Abstract• Background: Fluoroquinolones have a strong affinity with melanin, and their ocular effects have been reevaluated. Norfloxacin, one of the fluoroquinolones, has broad-spectrum activity against aerobic gram-positive and gram-negative bacteria. We examined the retinal toxicity and intraocular pharmacokinetics of intravitreal norfloxacin in rabbits. • Methods: Twenty-three albino and 23 pigmented rabbits were divided into three groups to evaluate retinal toxicity and two groups to investigate the intraocular pharmacokinetics. Each of these five groups was further divided into two subgroups (albino rabbits and pigmented rabbits). • Results: With 500 Etg norfloxacin, the oscillatory potential of the electroretinogram was transiently and selectively deteriorated in albino and pigmented rabbits, whereas the electroretinogram remained unchanged with 50 μg in pigmented rabbits. No changes were observed in the visual evoked potential or on histology of the retina 7 days after an intravitreal injection of 50 or 500 ltg norfloxacin. The electroretinogram and the retinal histology became abnormal 7 days after four intravitreal injections of 500 μg norfloxacin at 7-day intervals. As regards the intraocular pharmacokinetics after an intravitreal injection, the norfloxacin concentration in the chorioretina was as high as that in the vitreous 3 h after injection and was much higher than that in the vitreous 7 days after injection. Similar results were obtained after multiple injections. • Conclusion: These results indicate a high concentration of norfloxacin in the melanin-containing ocular tissues.

Nontoxic Intravitreal Dose of Ofloxacin for Rabbit Retina

We studied the nontoxic intravitreal concentration of ofloxacin, a new quinolone antibacterial agent, by evaluating its effects on in vitro and in vivo electroretinograms (ERGs) in albino and pigmented rabbits. After perfusion with a 36 micrograms/ml solution of ofloxacin, the in vitro ERG remained unchanged. The in vivo ERG and the visually evoked potential remained unchanged 4 weeks after vitrectomy with 50 micrograms/ml ofloxacin, and the retina was within normal limits both ophthalmoscopically and histologically. Therefore, the retinal toxicity of ofloxacin is low and within safe limits at clinical dosage.

Intraocular Kinetics of Ceftazidime (Modacin

The concentration of ceftazidime was determined in the aqueous humor and the vitreous body of normal, vitrectomized and aphakic/vitrectomized eyes and in the serum of albino rabbits 1 h after intravenous injection of 100 mg/kg ceftazidime. The intravitreal ceftazidime concentration was low (0.1-0.2 microgram/ml) in normal eyes 1 h after intravenous injection, and high (8.7 +/- 8.5 micrograms/ml) in vitrectomized and aphakic/vitrectomized eyes when injected immediately after surgery. The ceftazidime concentration was also determined in the aqueous humor and the vitreous body of normal eyes and in the serum of albino rabbits 3, 6, 12, 24 and 48 h after intravitreal injection of 200 micrograms. The intravitreal ceftazidime concentration after intravitreal injection decreased exponentially for 12 h (half-life about 7.4 h). It decreased more slowly thereafter and remained at 13.0 micrograms/ml (mean) even 48 h after injection. This concentration exceeded the minimum inhibitory concentrations against common gram-positive and gram-negative organisms causing endophthalmitis.

Intravitreal Flomoxef Sodium in Rabbits

We studied the intraocular concentration of flomoxef sodium in nonvitrectomized and vitrectomized eyes of albino rabbits after intravenous administration of 100 mg/kg flomoxef sodium. The concentration of flomoxef sodium in the vitreous body was undetectable (< 0.1 micrograms/ml) in nonvitrectomized eyes. Retinal toxicity of flomoxef sodium was investigated with ophthalmoscopy, electroretinography (ERG) and light microscopy after intravitreal injection of 200, 500, 1,000 and 2,000 micrograms flomoxef sodium in albino and pigmented rabbits. No ERG changes were induced with 200 micrograms. Other higher doses caused transient ERG changes. After the 200-micrograms injection, the intravitreal concentration decreased exponentially, the half-life being 4.4 h. The antibacterial activity, broad coverage and low intravitreal toxicity of flomoxef sodium suggest that this compound may be used to treat bacterial endophthalmitis.

Retinal toxicity and ocular kinetics of 1-β-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil in rabbits

The intraocular penetration of 1-β-d-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU), a new antiviral drug, after oral administration, the effects of non-toxic intravitreal doses of BV-araU, and the intraocular kinetics of BV-araU after intraocular injection were studied in rabbits. The intravitreal penetration of BV-araU after oral administration was very poor: 0.11 ± 0.13 μg/ml and 0.20 ±0.02 μg/ml respectively in albino and pigmented rabbits 2 h after 30 mg/kg. An intravitreal injection of 200 μg BV-araU caused transient electroretinographic (ERG) changes, whereas a 100-μg injection and intravitreal irrigation with 20 μg/ml BV-araU caused no ERG and histologic changes over the 4-week follow-up period. The half-life of the intravitreal concentration of BV-araU after an intravitreal injection was short (2.4 h). The results suggest that an intravitreal injection of 100 μg BV-araU or an intravitreal irrigating solution containing 20 μg/ml BV-araU is nontoxic to the retina and may be used for treatment of retinitis caused by varicella-zoster virus or herpes simplex virus type 1.

Topical Fluconazale: High Penetration without Corneal Toxicity

PURPOSE Fluconazole has been reported to effectively combat keratomycosis or Acanthamoeba keratitis. We investigated ocular penetration and comeal toxicity of topically administered fluconazole. METHODS Fluconazole (0.2%) was administered to albino rabbit eyes by instillations every 5 minutes for 1 hour, every 30 minutes for 12 hours, and by a single 0.3-ml subconjunctival injection. Control eyes received topical saline. Various ocular tissues and serum were sampled at various time points and assayed for fluconazole concentrations by high performance liquid chromatography (HPLC). Comeal epithelial and endothelial integrity after instillation was examined by specular microscopy and ultrasonic pachymetry. Lactate dehydrogenase (LDH) activity and protein concentration in the tears were determined by the methods of Wroblewski and of Bradford, respectively. Comeal epithelial healing rates in the fluconazole-treated and control eyes were examined by comeal photography after mechanical abrasion of the comeal epithelium. RESULTS 1) Fluconazole concentration was maximal in the conjunctiva, the cornea, the aqueous humor and the iris-ciliary body 15 to 30 minutes after the final instillation in the 1-hour regimen. 2) Fluconazole was detected in the conjunctiva, the cornea, the aqueous humor and the anterior lens cortex 1 hour after the 12-hour regimen. Comeal thickness, intraocular pressure, LDH activity or protein concentration in the tears were not significantly affected by fluconazole instillation. 3) Fluconazole was detected in the vitreous humor, the retinal pigment epithelium-choroid (RPE-choroid) and the sclera, except for the anterior ocular segments, after a subconjunctival injection. 4) The comeal epithelial healing rate did not significantly differ between the fluconazole-treated and control eyes. CONCLUSIONS The high intraocular concentrations and the lack of toxicity to the anterior ocular segments indicate that topical fluconazole is effective and safe for treating keratomycosis or Acanthamoeba keratitis.