Yuko Gohto

Macular Carotenoid Levels of Normal Subjects and Age-Related Maculopathy Patients in a Japanese Population

PURPOSE Macular carotenoid pigments composed of lutein and zeaxanthin are thought to affect the development of age-related maculopathy (ARM). Macular carotenoid levels were measured in normal Japanese subjects and Japanese patients with ARM. DESIGN Observational case-control series. PARTICIPANTS One hundred normal eyes of 100 normal subjects and 187 eyes of 97 patients with ARM; all were Japanese. The definitions of early ARM and late ARM (exudative age-related macular degeneration [AMD] and dry AMD) were used according to an accepted international classification system. METHODS Macular carotenoid levels were measured using resonance Raman spectroscopy. MAIN OUTCOME MEASURE Raman signal intensity generated from carbon-carbon double bond vibrations of lutein and zeaxanthin. RESULTS The mean (+/-standard deviation [SD]) macular carotenoid level in normal subjects was 1471+/-540 Raman counts. The macular carotenoid levels in normal subjects declined with age. The mean macular carotenoid level was 620+/-204 (+/-SD) in eyes with early ARM and 427+/-283 (+/-SD) in eyes with late ARM (equal to AMD). The macular carotenoid levels of early ARM and AMD were significantly lower than those in normal subjects older than 60 years (1100+/-340 [+/-SD]). No difference was revealed in carotenoid levels by the severity for ARM, type of AMD (exudative, atrophic, and disciform scar), or types of choroidal neovascularization (classic, minimally classic, occult, polypoidal choroidal vasculopathy), although small numbers in some groups weakened statistical power. Macular carotenoid levels were affected by the severity of macular disease in the opposing eye. The average for normal eyes where AMD was found in the opposite eye was significantly lower than that of normal eyes in the absence of AMD in the opposite eye (i.e., healthy volunteers older than 60 years). CONCLUSIONS Macular carotenoids decreased even in older healthy individuals. The ARM patients showed lower macular carotenoid levels than healthy people. Low macular carotenoid levels may be one of the risk factors of progression in ARM.

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.

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).

Macular Pigment Changes in Pseudophakic Eyes Quantified with Resonance Raman Spectroscopy

PURPOSE We examined changes in macular pigment optical density (MPOD) levels after cataract surgery and compared the MPOD between eyes with clear intraocular lenses (IOLs) and yellow-tinted IOLs. DESIGN Prospective, comparative case series. PARTICIPANTS The MPOD levels were measured in 480 eyes of 337 patients after cataract surgery. Among them, the data from 259 eyes (clear IOL group, 121 eyes; yellow-tinted IOL group, 138 eyes) of 259 Japanese patients were selected for statistical analyses on the basis of the inclusion criteria: a postoperative visual acuity (VA) of ≥0.8 and no fundus diseases. Only 1 eye of each patient was enrolled. Patients provided informed consent to participate in this study on the basis of the approval of the institutional review board before surgery. METHODS The patients selected the type of IOL to be implanted. The MPOD levels were measured using resonance Raman spectroscopy on day 1 (baseline value); months 1, 3, and 6; and years 1 and 2 postoperatively. MAIN OUTCOME MEASURES The difference in MPOD levels between the IOL groups was analyzed by unpaired t tests. The following parameters were analyzed by multiple regression analysis: age, gender, body mass index (BMI), smoking history, glaucoma, diabetes, preoperative VA, preoperative refractive error, and IOL power and type. RESULTS We found no significant differences in the baseline characteristics between the 2 groups. Until 6 months postoperatively, the MPOD levels did not differ significantly between the groups. However, from 1 year onward, the levels were significantly higher in the yellow-tinted IOL group compared with the clear IOL group. By multiple regression analysis, 1 day postoperatively, older age and diabetes were correlated with lower MPOD levels; 1 year postoperatively and thereafter, however, lower MPOD levels were correlated with clear IOLs. CONCLUSIONS Cataract surgery with clear IOLs induced a greater decrease in macular pigment levels compared with yellow-tinted IOLs during a longer follow-up period. These findings agreed with observations that excessive light exposure is associated inversely with MPOD, because clear IOLs transmit higher intensities of blue light than yellow-tinted IOLs.

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.

Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements.

Purpose To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. Methods Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured. Results The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. “retinal responders”, who had an increase of both MPOD levels and serum lutein concentrations (n = 13), “retinal non-responders”, who had only increased serum concentrations and no change in MPOD levels (n = 20), and “retinal and serum non-responders”, who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in contrast sensitivity. Conclusions No statistically significant differences could be detected for MPOD levels and serum lutein concentrations between the two investigated lutein supplement formulations. Responses to lutein supplementation regarding MPOD levels and serum lutein concentrations varied between subjects. Subjects with lower MPOD levels at baseline responded well to lutein supplementation. However, since the number of subjects was low, a further study with more subjects is needed to prove that subjects with low MPOD levels will benefit from lutein supplementation. Trial Registration UMIN-CTR UMIN000004593

Autofluorescence imaging of macular pigment: influence and correction of ocular media opacities.

Abstract. The healthy adult human retina contains in its macular region a high concentration of blue-light absorbing carotenoid compounds, known as macular pigment (MP). Consisting of the carotenoids lutein, zeaxanthin, and meso-zeaxanthin, the MP is thought to shield the vulnerable tissue layers in the retina from light-induced damage through its function as an optical attenuator and to protect the tissue cells within its immediate vicinity through its function as a potent antioxidant. Autofluorescence imaging (AFI) is emerging as a viable optical method for MP screening of large subject populations, for tracking of MP changes over time, and for monitoring MP uptake in response to dietary supplementation. To investigate the influence of ocular media opacities on AFI-based MP measurements, in particular, the influence of lens cataracts, we conducted a clinical trial with a large subject population (93 subjects) measured before and after cataract surgery. General AFI image contrast, retinal blood vessel contrast, and presurgery lens opacity scores [Lens Opacities Classification System III (LOCS III)] were investigated as potential predictors for image degradation. These clinical results show that lens cataracts can severely degrade the achievable pixel contrasts in the AFI images, which results in nominal MP optical density levels that are artifactually reduced. While LOCS III scores and blood vessel contrast are found to be only a weak predictor for this effect, a strong correlation exists between the reduction factor and the image contrast, which can be quantified via pixel intensity histogram parameters. Choosing the base width of the histogram, the presence or absence of ocular media opacities can be determined and, if needed, the nominal MP levels can be corrected with factors depending on the strength of the opacity.

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.

Effect of age and other factors on macular pigment optical density measured with resonance Raman spectroscopy

Background Macular pigment is a defense system against phototoxic damage of the retina by visible light. It is still under debate whether or not macular pigment optical density (MPOD) levels decline with age, because the age effect varied depending on the technique used to measure MPOD levels. Resonance Raman spectroscopy (RRS) is an objective method to measure MPOD, and studies using RRS showed a drastic age-related decline of MPOD levels; however, since RRS measurements are influenced by cataracts, it has been argued that the age-related decline of RRS measurements is an artifact from lens changes in aged subjects. In the present study, MPOD levels were measured with RRS in pseudophakic eyes, and the effects of age and other factors on MPOD levels were investigated.