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Autofluorescence and advanced glycation end product (AGE) levels were measured in the lenses of 9 diabetic Chinese hamsters and 6 age-matched controls. Lens autofluorescence also was measured in 37 diabetic patients and 14 age-matched controls. Lens autofluorescence values were measured noninvasively with a lens measurement system using color filters with peak transmission at 365- and 434-nm wavelengths (excitation and emission, respectively) that are characteristic of AGE fluorescence. The peak lens autofluorescence level was used as the lens autofluorescence value, and the mean lens autofluorescence values from both eyes of each subject were used for statistical analysis. The AGE levels in one lens from each hamster were measured by noncompetitive enzyme-linked immunosorbent assay with a polyclonal anti-AGE antibody. We found a 2.2 times increase of the mean lens autofluorescence value of diabetic hamsters in comparison with that of controls (P

To study the early ocular abnormalities in young diabetic patients, corneal and lens autofluorescence was measured by fluorophotometry in 30 eyes of 30 insulin-dependent diabetic patients without retinopathy. The lens [f(l)] and the corneal [f(c)] autofluorescence values in diabetic patients were significantly higher than in controls. In diabetic patients, f(l) was significantly correlated with the duration of diabetes, the f(c) was significantly correlated with the duration of diabetes and the indices of metabolic control, i.e. HbA1c and fructosamine. Our study demonstrated that young diabetic patients clearly had corneal and lens abnormalities before the appearance of overt diabetic retinopathy. The f(c) value might be a good indicator of metabolic control in diabetic patients.

We developed a tree shrew model of diabetes using streptozotocin (STZ), and studied early ocular changes of diabetes (after one week of diabetes) by fluorophotometry. STZ was injected intraperitoneally at doses of sixty to 400 mg/kg body weight. Animals injected with more than 300 mg/kg of STZ developed diabetes. Corneal autofluorescence was significantly increased one week after STZ injection. These changes may be related to impairment of the ocular homeostatic mechanisms due to the onset of diabetes. Using this model, we might be able to obtain diabetic ocular impairment data closer to human data than in previous models of diabetes, because tree shrews are primates.

The effects of topically applied timolol (a nonselective beta-blocker) and UF-021 (a prostaglandin-related compound) on pulsatile ocular blood flow (POBF) were investigated in 9 healthy volunteers. One drop of either UF-021 or timolol was instilled in one randomly selected eye and the fellow eye received physiologic saline. Before and 90 min after drop instillation, we measured intraocular pressure (IOP), POBF, heart rate (HR) and blood pressure (BP). After a washout interval of at least 1 week, the other drug was instilled in the previously treated eye. IOP, POBF, HR, and PB were measured following the same protocol. After timolol administration, IOP and POBF decreased significantly in the treated eye (26%, p = 0.01, and 13%, p = 0.02, respectively) and in the fellow eye (11%, p = 0.01, and 11%, p = 0.03, respectively). HR also decreased (10%, p = 0.03), but BP did not change significantly. After UF-021 administration, no significant changes were found in IOP, POBF, HR, or BP. Our results suggest that in normal subjects timolol decreases POBF in both the treated and the untreated eyes, whereas UF-021 has no action on either IOP or POBF.

We investigated corneal and lens autofluorescence in patients with proliferative diabetic retinopathy (PDR) to determine a correlation between the two parameters and blood glucose levels and HbA1c.Corneal and lens autofluorescence levels in 17 PDR patients and 8 healthy controls were measured with a fluorophotometer fitted with an anterior segment adapter. We measured the lower blood glucose level (BS1), corneal autofluorescence (CA1), and lens autofluorescence (LA1) simultaneously and the higher blood glucose level (BS2), CA2, and LA2 simultaneously on the same day. We defined parameter changes as: delta BS = BS2 - BS1, delta CA = CA2 - CA1, and delta LA = LA2 - LA1.Corneal and lens autofluorescence significantly increased in the patients, compared with the controls (p0.001). Lens autofluorescence had a significant positive correlation with HbA1c (r = 0.656, p0.01) in the patients. delta CA (ngEq/ml) correlated significantly with delta BS (mg/dl) (r = 0.631, P0.01).Results suggest that lens autofluorescence might represent the long-term control of diabetes, and corneal autofluorescence levels may represent short-term changes in the blood glucose level, because hyperglycemia accelerates with increasing corneal autofluorescence in PDR patients. Corneal and lens autofluorescence may be related to the breakdown of the blood-aqueous barrier.

OBJECTIVE—To evaluate corneal advanced glycation end product (AGE) fluorescence in patients with diabetes and in healthy control subjects. RESEARCH DESIGN AND METHODS—Corneal autofluorescence was measured in 26 eyes of 26 patients with type 2 diabetes (mean age 57.0 years; mean disease duration 12.2 years; mean HbA1c 7.1%) and 13 eyes of 13 healthy age-matched control subjects (mean age 57.9 years). The patients with type 2 diabetes were divided into the following groups: patients without diabetic retinopathy (DR), patients without proliferative diabetic retinopathy (PDR), and patients with PDR. Corneal autofluorescence was measured by fluorophotometry with the wavelength that is characteristic of AGE fluorescence (excitation and emission 360–370 nm and 430–450 nm, respectively). We defined peak corneal autofluorescence levels as corneal AGE fluorescence values. We compared the corneal AGE fluorescence values in the four groups. RESULTS—In the PDR group (11.9 ± 3.9 arbitrary units [mean ± SD]), the corneal AGE fluorescence values were significantly higher compared with the control subjects (6.9 ± 1.3 arbitrary units), the patients without DR (7.4 ± 2.1 arbitrary units), and the patients without PDR (6.9 ± 2.2 arbitrary units) (P < 0.05). CONCLUSIONS—We found that corneal AGEs may increase in patients with diabetes and PDR compared with control subjects, patients without DR, and patients without PDR. In the patients with PDR, increased corneal AGEs may play a role in diabetic keratopathy.

Purpose To examine the diurnal variations in corneal autofluorescence in normal and diabetic patients. Methods We measured corneal autofluorescence using a fluorophotometer fitted with an anterior segment adapter. Corneal autofluorescence was measured 10 times at 3 min intervals to evaluate the reproducibility of this instrument in 4 eyes of 4 normal subjects. The diurnal variation in corneal autofluorescence was determined by measuring the fluctuations in 10 eyes in 10 normal subjects and one unoperated eye each of 10 patients with proliferative diabetic retinopathy (PDR). We performed five consecutive measurements at 1000, 1130, 1400, 1630 and 1900 hours. The mean value of five measurements, the variation range and the coefficient of variation were analysed. Results The mean coefficient of variation in the measurement using this instrument was 8.6 ± 1.0%. In the patients with PDR, the mean corneal autofluorescence value was significantly higher (p < 0.001), the variation range was significantly wider (p < 0.001) and the coefficient of variation was significantly greater (p < 0.01) than in the normal subjects. Conclusions The results of this study suggest that corneal autofluorescence changes over the course of a day in patients with diabetes. This may be caused by the breakdown of the blood-aqueous barrier that we reported previously.

The object of this study was to clarify the ocular structural changes of tree shrews during development and the influence of growth on experimental myopia. Eighty-four eyes of 42 tree shrews (43–1604 days old) were included. The body weight was measured. The axial length was measured using A-mode ultrasonography, and the mean value of both eyes was calculated. Monocular form deprivation (FD) was induced in 13 8-week-old tree shrews. The axial length and refractive error were measured before and at 15, 30,45, 60, 90, and 120 days after FD was induced. The body weights increased rapidly from birth until 100 days, the point at which tree shrews reach maturity. The ocular structures changed rapidly during this period, except for the anterior chamber depth. In the animals with FD, myopia increased rapidly by 45 days following FD at approximately 100 days after birth. However, after this time, myopia increased slowly. Almost the same results were found for the vitreous cavity and the axial length. Our study demonstrated that ocular structural growth changes markedly to the point at which tree shrews reach maturity, and FD myopia may be influenced by ocular growth.

The purpose of this study was to evaluate the correlation between corneal and lens autofluorescence and the various degrees of myopia. Forty-five eyes of 45 myopic patients (mean age ± SD, 23.8 ± 2.4 years; range, 18 to 27 years) were included. Subjects wearing contact lenses were excluded. After inducing mydriasis, we mea¬sured corneal and lens autofluorescence levels, refractive error, and axial length. A significant correlation was found between refractive error and length of the vitreous cavity. Neither anterior chamber depth nor lens thickness correlated with refrac¬tive error. Refractive error was significantly correlated with corneal and lens autofluorescence levels (r = 0.415, P 0.0005). Corneal and lens autofluorescence levels increased as the axial length increased in myopic eyes. This increase may be related to the breakdown of the blood-ocular barrier that we previ¬ously reported.

The purpose of this work was to study the influence of gender in tree shrew eyes with growth and experimental myopia. Ocular components were measured using A–mode ultrasonography in 63 eyes of 63 tree shrews (38 females and 25 males, ages 43–1542 days). Twenty 8–week–old tree shrews (11 males and 9 females) were monocularly fitted with a translucent goggle 3 weeks after eye opening. Optical refractions were also measured using a refractometer. Measurements were performed before and 15 days after form deprivation (FD) was induced. In normally developing male and female tree shrews, the same growth pattern of the ocular components was observed. In experimental myopia, compared with the paired normal eyes, FD eyes were myopic, and the vitreous cavity and axial length were longer in both genders. When myopic changes in FD eyes were compared with control eyes, no statistically significant differences were found based on gender. In tree shrews, gender has no effect on developing eyes and experimental myopia in a comparison of FD eyes and paired controls.

Lenticular autofluorescence was measured in vivo in 25 normal tree shrews using a fluorophotometer with a specially designed small animal adapter to assess the usefulness of this model of lens pathology. The average variability in the lenticular autofluorescence measurements was 8.7%. The average ratio between lenticular autofluorescence of the left eye and that of the right eye was 0.99 +/- 0.13 SD. There was a strong correlation between age and mean lenticular autofluorescence in both eyes (correlation coefficient, 0.988; p0.001). The calculated annual increase in lenticular autofluorescence was 23.7 ngEq/ml. This method of measurement is reliable, and lenticular autofluorescence in tree shrews varies little among animals other than a variation caused by aging. Moreover, the tree shrew, which is believed to be a primate, is small and easy to breed. This could be a useful animal model to study various lens pathologies in humans.

To study the correlation between blood–retinal barrier (BRB) permeability and development of form deprivation (FD) myopia, FD was induced in tree shrews. The refractive error and the axial dimensions of the optical elements were measured. Ocular fluorescence was measured before and after fluorescein-Na injection. The inward permeability (Pin) of the BRB was measured before and 15, 30, and 45 days after FD was induced. FD eyes became significantly myopic 15 days after FD was induced (P