Akira Obana

Indocyanine Green Angiographic Aspects Of Multiple Evanescent White Dot Syndrome

Purpose The authors investigated the indocyanine green angiography findings of multiple evanescent white dot syndrome (MEWDS). Methods Four patients with MEWDS underwent examination by indocyanine green angiography, conventional ophthalmoscopy, and fluorescein angiography. Results Fundus examination showed multiple white dots in the retinal pigment epithelium of the unilateral eye of each patient. Fluorescein angiography demonstrated early hyperfluorescence corresponding to the white dots. In the early phase, indocyanine green angiography showed no abnormal signs in the large choroidal vessels, but in the late phase, hypofluorescent lesions appeared, corresponding to the white dots. The hypofluorescent dots were clustered in the posterior pole and sporadic in the peripheral region, appearing to radiate away from the optic disc or fovea. The hypofluorescent dots disappeared at the recovery stage. Conclusions Previous fluorescein angiographic and electrophysiologic studies have demonstrated the involvement of the retinal pigment epithelium (RPE) and photoreceptors in MEWDS. The current findings on indocyanine green angiography suggest that MEWDS affects the choriocapillaris or precapillary arterioles as well as the RPE and photoreceptors, and that the lesions spread to the midperipheral region, centering on the optic disc or fovea.

Management of orbital lymphangioma using intralesional injection of OK-432

AIM To treat orbital lymphangioma with an intralesional injection of OK-432 (group AStreptococcus pyogenes of human origin). METHOD A 14 year old boy had a right orbital cystic lymphangioma. The visual acuity in the eye was 20/28. In an initial treatment, 0.02 mg of OK-432, was injected into the tumour after aspiration of the fluid contents, but no effect was seen. The second treatment was performed with 0.04 mg of OK-432. RESULT 4 months later, the lesion had totally shrunk to fibrous tissue. The side effects were fever, a local inflammatory reaction lasting 3 days, and increased intraocular pressure, which was managed by draining the fluid contents. Visual acuity improved to 20/15, and the visual field defect and restriction of eye movement seen before treatment disappeared. No recurrence was noted 1 year after treatment. CONCLUSION An intralesional injection of OK-432 shrunk the lymphangioma without functional disturbance and scar in the facial skin. OK-432 may be useful for orbital lymphangioma, but further studies are still warranted to determine efficacy, complications, and the optimal dose for safe treatment.

Photodynamic Therapy for Experimental Tumors Using ATX‐S10(Na), a Hydrophilic Chlorin Photosensitizer, and Diode Laser

ATX‐S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second‐generation photosensitizer for use in photodynamic therapy (PDT) for cancer treatment. The effectiveness of PDT using ATX‐S10(Na) and a diode laser for experimental tumors was evaluated in vitro and in vivo. In‐vitro PDT using ATX‐S10(Na) and the diode laser showed drug concentration‐, laser dose‐ and drug exposure time‐dependent cytotoxicity to various human and mouse tumor cell lines. In Meth‐A sarcoma‐implanted mice, optimal PDT conditions were found where tumors were completely eliminated without any toxicity. Against human tumor xenografts in nude mice, the combined use of 5 mg/kg ATX‐S10(Na) and 200 J/cm2 laser irradiation 3 h after ATX‐S10(Na) administration showed excellent anti‐tumor activity, and its efficacy was almost the same as that of PDT using 20 mg/kg porfimer sodium and a 100 J/cm2 excimer dye laser 48 h after porfimer sodium injection. Microscopic observation of tumor tissues revealed that PDT using ATX‐S10(Na) and the diode laser induced congestion, thrombus and degeneration of endothelial cells in tumor vessels, indicating that a vascular shutdown effect plays an important role in the anti‐tumor activity of PDT using ATX‐S10(Na) and the diode laser.

Selective occlusion of choroidal neovascularization by photodynamic therapy with a water-soluble photosensitizer, ATX-S10

To determine the optimal treatment parameters for selective occlusion of choroidal neovascularization (CNV) by photodynamic therapy (PDT) by using the photosensitizer ATX‐S10 and a diode laser (wavelength = 670 nm).

In vitro Plasma Protein Binding and Cellular Uptake of ATX‐S10(Na), a Hydrophilic Chlorin Photosensitizer

ATX‐S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second‐generation photosensitizer for photodynamic therapy (PDT) for cancer treatment. In this study, we examined plasma protein binding, cellular uptake and subcellular targets of ATX‐S10(Na) in vitro. Protein binding ratios of 50 μg/ml ATX‐S10(Na) in rat, dog and human plasma were 73.0%, 87.2% and 97.7%, respectively. Gel filtration chromatography revealed that 1 mg/ml ATX‐S10(Na) bound mainly to high‐density lipoprotein (HDL) and serum albumin at the protein concentration of 0.4%, with binding ratios of 46% and 36%, respectively. The free form of ATX‐S10(Na) was mostly incorporated into T.Tn cells, and its cellular uptake was partially but significantly inhibited by endocytosis inhibitors such as phenylarsine oxide, chloroquine, monensin and phenylglyoxal, and by chilling the cells to 4°C. However, ouabain, harmaline, sodium cyanide, probenecid and aspartic acid did not influence the uptake of ATX‐S10(Na), suggesting that cellular uptake of ATX‐S10(Na) was not related to sodium‐potassium pump activity, sodium‐dependent transporter activity, mitochondrial oxidative respiration, organic anion transporter activity or aspartic acid transporter activity. By fluorescence microscopy, lysosomal localization of ATX‐S10(Na) was observed in T.Tn cells. However, electron microscopic observation revealed that many subcellular organelles such as mitochondria, endoplasmic reticulum, ribosomes, Golgi complex and plasma membrane were damaged by PDT using 25 μg/ml ATX‐S10(Na) soon after laser irradiation at 50 J/cm2, and tumor necrosis was rapidly induced. This result indicated that ATX‐S10(Na) was widely distributed within the cell.

Computer assisted image analysis using the subtraction method in indocyanine green angiography

The choroidal vessels are three dimensionally distributed and very complex in their patterns. They often appear to be overlaid in indocyanine green (ICG) angiograms so it is harder to analyze ICG angiography than fluorescein angiography. When an earlier frame is subtracted from a later frame in a sequence of angiograms, the fluorescence which has increased during the time between the two frames can theoretically be demonstrated. We applied computer-assisted image subtraction methods in selected clinical cases of directly acquired digital ICG angiography to demonstrate how this method works. We used software already installed in an IMAGEnet computer system (Topcon) for image subtraction. We applied the subtraction technique in 18 cases with various diseases. When two images with a time difference of several seconds were subtracted, filling of the choriocapillaris, the neovascularization or the pathological vessels could be observed. When the images had a time difference of several minutes, intrachoroidal dye leakage could be seen more clearly. This method is very helpful for analyzing pathological changes in ICG angiography in clinical cases, when two images are selected appropriately.

Photodynamic Therapy for Corneal Neovascularization Using Topically Administered ATX-S10(Na)

BACKGROUND AND OBJECTIVE We investigated the effect of photodynamic therapy (PDT) using topically administered ATX-S10(Na) on corneal neovascularization (CoNV). MATERIAL AND METHODS Rabbit eyes with induced CoNV were treated with ATX-S10(Na) eye drops (10 mg/mL) every 5 minutes, 5 to 25 times. Five to ninety minutes after topical administration, the CoNV were irradiated with a diode laser using a wavelength of 670 nm. RESULTS The CoNV were occluded fluorescein angiographically in 7 of 16 treated eyes. The eyes having occluded, CoNV were irradiated using fluence of 510-1019 J/cm2 within 20 minutes of eye-drop administration. However, the effect was more variable than what we found using systemic administration in our previous investigation. CONCLUSIONS Experimental CoNV was occluded by photodynamic therapy using topically administered ATX-S100(Na), suggesting this modality as a possible treatment for CoNV avoids the side effects found with systemic administration of the dye. Further efforts to improve the eye drops in terms of pH and osmotic pressure are needed to achieve increased dye accumulation.

Long-term effectiveness of photodynamic therapy by using a hydrophilic photosensitizer ATX-S10(Na) against experimental choroidal neovascularization in rats

We previously demonstrated that a hydrophilic photosensitizer ATX‐S10 had a potent photodynamic effect. This study was designed to reveal the long‐term effectiveness of photodynamic therapy (PDT) with this agent in occluding choroidal neovascularization (CNV) and its selectivity in the neovascular tissue.

Indocyanine green angiographic features prognostic of visual outcome in the natural course of patients with age related macular degeneration

AIMS To determine indocyanine green (ICG) angiographic features prognostic of visual acuity loss in eyes following a natural course of exudative age related macular degeneration (AMD). METHODS 89 eyes of 72 patients (48 men, 24 women) aged between 50 and 87 years old (mean 69.5 (SD 8.8) years) with classic and/or occult choroidal neovascularisation (CNV) were reviewed. ICG angiographic features were classified as follows: type 1, well demarcated hyperfluorescence with late ICG leakage; type 2, well demarcated hyperfluorescence with no late dye leakage; type 3, poorly demarcated hyperfluorescence; type 4, no hyperfluorescence. Follow up ranged from 6 to 67 months (mean 19.2 (11.5) months). Logistic regression analyses were performed using change of visual acuity (worse or not) as the dependent variable, and patient age, sex, characteristics of fluorescein angiography (classic or occult CNV), location of CNV, and each ICG type as the independent variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS Type 1 CNV was associated with the highest risk for visual acuity loss (OR: 7.50, CI: 1.42–39.55, p=0.018) among the present variables. In contrast, CNV having no ICG leakage (type 2, 3, and 4), represented no significantly increased risk. CONCLUSION Well demarcated hyperfluorescence with late ICG leakage appears to be predictive of visual acuity loss in eyes with CNV. Thus, ICG angiography may offer a useful means of predicting visual outcomes in AMD.

Treatment Parameters for the Efficacy of Transscleral Cyclophotocoagulation in Rabbits Using a Diode Laser

PURPOSE To determine parameters for the efficacy of transscleral cyclophotocoagulation (TSCPC) using a diode laser. METHODS We performed TSCPC on 74 pigmented rabbits with different exposure powers and varying number of applications, followed by clinical observation and histological examination up to 24 weeks. RESULTS Based on observation of the clinical course, the most favorable parameters were 600 mW and 36 or 48 applications, which did not cause severe complications and sufficiently lowered intraocular pressure (IOP). Histological examination revealed coagulation of the epitheliums and stroma of the ciliary body at 600 mW. The stroma of the ciliary body was severely damaged at 900 mW. CONCLUSIONS Transscleral cyclophotocoagulation at 600 mW with a larger number of applications than previously reported did not cause severe complications and effected greater and more lasting lowering of IOP than TSCPC with more intense coagulation and fewer applications.