Early retinal and renal abnormalities in diabetes.

The integrity of the blood-retinal and blood-glomerular vascular barriers were investigated simultaneously in diabetic individuals to determine whether or not the early forms of diabetic retinopathy and nephropathy are temporally related. The blood-retinal barrier was assessed by the technique of vitreous fluorophotometry. Twenty-four hour urinary excretion of albumin was determined by radioimmunoassay before fluorescein measurement. Posterior vitreous fluorescein leakage was greater in the study cohort than in the control population after diabetes had been present 11-20 years (p < 0.05) and 21 years or more (p < 0.01). Albumin excretion was also increased in the diabetic subjects (p < 0.001) and correlated to duration of diabetes (r = 0.51, p < 0.005). Hypertension raised midvitreous fluorescein levels (p < 0.05), but it had no effect on posterior vitreous values. Hypertension was an independent predictive factor for urinary albumin excretion (p < 0.05). Partial correlation analysis showed that vitreous fluorescence and urinary protein were not significantly correlated when controlled for duration of diabetes and for age. Early proteinuria did not predict retinal vascular leakage, nor did increased fluorescein leakage predict renal decompensation in the diabetic subjects. The data suggest that during the early stages of retinal and renal abnormalities associated with insulin-dependent diabetes, the eye and kidney follow different temporal courses to abnormal function.

Retinal sensitivity in acute hypoglycemia.

We measured retinal threshold sensitivity via automated computerized static perimetry in predetermined meridians in euglycemic diabetic subjects and in the same subjects during insulin-induced hypoglycemia. During periods of reduced blood glucose levels, decreased retinal sensitivity, most marked in temporal meridians, was observed.

Ageing parameters of the ocular lens by scanning fluorophotometry.

A Beer-Lambert analysis of fluorophotometric scans of ocular lenses has been carried out. It is shown that an assumption of a single flourophor allows us to calculate the distribution of this fluorophor along the central lens axis. For the great majority of lenses in our study, covering a wide range of ages, our results are in essential agreement with published results on excised lenses. For a small subset of lenses in the study the assumption of a single fluorophor is found to be unsatisfactory. In these cases a reasonable symmetry assumption allows us to estimate the distribution of an additional agent which removes light from the entering or exiting beams without contributing to the fluorescence. The fact that this agent is restricted to the lens nucleus and that it occurs in lenses in which nuclear changes are clinically evident suggests that it is an expression of nuclear cataract.

Fluorophotometric measurement of human tear turnover rate.

Measurement of tear turnover rate using an automated scanning fluorophotometer (FluorotronR) was compared to Schirmer test results without anesthesia in young adults with no known ocular disorder. After the instillation of fluorescein, tear film fluorescence, expressed as fluorescein concentration equivalent, decreased exponentially in a linear fashion with time. The mean tear turnover rate was 30% per minute. Contact lens wearers had higher mean tear turnover rates when compared with non-contact lens wearers, but differences were not statistically significant. Half of tested eyes demonstrated total wetting of Schirmer Tear Test StripsR. Higher mean tear turnover rates were associated with complete wetting of the Schirmer test strips. There was no significant correlation between Schirmer paper wetting of less than 30 mm and fluorescein turnover rate.

Delayed retinal effects of the frequency-doubled YAG laser (532 nm).

In order to compare the retinal effects of the frequency-doubled YAG laser (532 nm) with those of argon laser, rabbit eyes were exposed to green YAG laser irradiation and processed for light and electron microscopic study at 24 hr, 2 weeks and 4 weeks. Detailed analysis was conducted on tissue exposed to 7.3 and 7.6 millijoules (mj). Response of the photoreceptors and retinal pigmented epithelium to green YAG was very similar to that described for argon laser over the same time period. By 2 weeks post-exposure, there was histologic evidence of partial recovery with absence of damaged, pycnotic photoreceptor nuclei, increased numbers of typical photoreceptor outer segment lamellae and repair of retinal pigmented epithelium. Four weeks after irradiation, normal-appearing photoreceptor nuclei were present although inner photoreceptor segments still showed mitochondrial damage. Outer segments at 4 weeks showed regular lamellar structures. We conclude that the frequency-doubled YAG laser is equivalent to the argon laser with respect to the production of thermal lesions in the retina. Its additional advantages include increased efficiency, portability, reliability and lack of absorption by macular xanthophyll pigment.

Autofluorescence of the crystalline lens in diabetes.

Lenticular autofluorescence in a diabetic population was quantitated by scanning ocular fluorophotometry. Measurements were made through the lens along the optical axis. The profile of the scan from front to rear was characterized by anterior and posterior juxtacortical peaks and a central plateau. Maximum fluorescence values were compared with those of nondiabetic control subjects. Fluorescence increased linearly with age in both populations, but was significantly higher in the diabetic population of all ages. Posterior to anterior fluorescence peak ratios decreased as a parabolic function of age in both populations, but peak ratios were lower in the diabetic population. We conclude that in vivo measurements of lens autofluorescence correlate with premature lenticular senescence in diabetes.

Increased synthesis of glycosaminoglycans of the cornea during fasting and refeeding in rats.

The effect of a 48 hour fast on sulfate incorporation of corneal mucopolysaccharides was investigated in the rat. After fasting for 24 hours, experimental and control rats were injected intraperitoneally with 35S-sulfate. After fasting an additional 24 hours, the rats were sacrificed and incorporation of the label into the acid mucopolysaccharide fraction of the cornea was determined. Incorporation of the label into the acid mucopolysaccharide fraction was significantly increased in the fasted rat cornea. Increased synthesis of corneal sulfated mucopolysaccharides during fasting in the rat contrasts with the well known decreased synthesis in cartilage under the same conditions. These findings suggest that corneal acid mucopolysaccharide synthesis is selectively preserved and/or increased during fasting.

Autofluorescence and light transmission in the aging crystalline lens.

We quantitated blue-green light transmission and autofluorescence of the human crystalline lens in vivo, using an automated scanning fluorophotometer (Fluorotron) coupled with a lens system designed for high resolution of the ocular anterior segment. Lenses were scanned through the dilated pupil along the optical axis, generating a fluorescence profile consisting of anterior and posterior juxtacortical peaks and a central plateau. Fluorescence increased linearly with increasing age. We calculated percent transmission of excitation (410-500 nm) and emission (510-670 nm) as the ratio of posterior to anterior juxtacortical peaks. Light transmission decreased as a parabolic function of age and was correlated with both fluorescence increase and observed lens brunescence.

Anterior retinal cryotherapy in diabetic vitreous hemorrhage.

Recurrent vitreous hemorrhage associated with proliferative retinopathy can occur in eyes that do not satisfactorily respond to argon laser pantretinal photocoagulation. To evaluate the effect of relatively low-risk surgical intervention, we performed peripheral retinal cryopexy on 24 eyes of 23 diabetic patients with proliferative diabetic retinopathy and vitreous hemorrhage. In most cases, cryopexy followed complete or nearly complete panretinal photocoagulation which did not prevent subsequent vitreous hemorrhage. Existing vitreous hemorrhage cleared postoperatively in 23 of 24 eyes. The best corrected visual acuity improved in 15 eyes, remained unchanged in five, and worsened in four. Four postoperative anterior segment complications resolved completely within a short time. One patient, a 68-year-old woman who had had diabetes for 18 years, postoperatively had a macular hole in one eye and macular edema with tractional retinal detachment in the other.

Retinal cryopexy in the management of proliferative diabetic retinopathy.

Peripheral retinal cryopexy resulted in stabilization of progressive retinopathy and vitreous hemorrhage in 13 eyes of 13 diabetics. In most cases, cryopexy followed complete or nearly complete pan-retinal photocoagulation which did not prevent subsequent vitreous hemorrhage. No eyes in our series hemorrhaged following cryopexy during the period of postoperative observation. Existing vitreous opacities generally cleared sufficiently to permit further photocoagulation. Visual acuity did not decrease on the basis of hemorrhage after cryotherapy, but rather improved in most cases. Peripheral retinal cryopexy is recommended as an alternative to vitrectomy for the initial treatment of recurrent and persistent diabetic vitreous hemorrhage.

Factors affecting vitreous fluorescence.

A variety of mechanical (intensity of the light source, the width and the angle of the exciting source) and physiological factors (retinal pigmentation, vitreous fluorescence) and many systemic factors affect the results of vitreous fluorophotometry. These factors are discussed with respect to identifying those that are inconsequential and those that are significant. Methods to compensate for the important factors are described.

Optimized protocol for Fluorotron Master.

The technical aspects of fluorophotometry equipment are presented. The sources of artifact are described and a protocol to optimize the use of the "Coherent Fluorotron Master" system is presented. The results of fluorophotometry studies on ten patients indicate that more accurate data evaluation can be achieved using this approach.

Identification of the pre-proliferative diabetic eye.

The rationale for early identification of the stage of diabetic retinopathy immediately preceding development of fibrovascular proliferation is that early diagnosis affords the opportunity to treat by photocoagulation or other methods at the appropriate stage of retinal disease. Aids to identification include: venous abnormalities, intraretinal microvascular abnormalities, "cotton-wool" spots and fluorescein angiographic evidence of capillary non-perfusion. Although no one of these fundus changes is specific for the pre-proliferative stage of diabetic retinopathy, the presence of more than one of these findings increases the risk of subsequent fibrovascular proliferation. The development of frank proliferation frequently occurs within two years of first appearance of the preproliferative stage.

Retinal effects of the frequency-doubled (532 nm) YAG laser: histopathological comparison with argon laser.

Retinal lesions produced in Dutch Cross rabbits with a frequency-doubled (532 nm) YAG laser in single pulse mode (30-100 microJ) and in train of uniform pulses (2.6 and 7.5 mJ) underwent histopathological examination by light and electron microscopy. The results were compared to argon laser lesions (11 and 15 mJ) in the same animals. Low-energy single-pulse YAG lesions produced separation of the neural retina from the retinal pigmented epithelium (RPE), while higher energies caused severe disruption of retinal structures with moderate damage to the RPE. A striking and consistent finding of all the single-pulse lesions was the presence of red blood cells between the RPE and neural layers. The findings appear to support a process of mechanical disruption. In contrast, the lesions produced by a uniform train of pulses showed well-defined damage to RPE and photoreceptors with no red blood cells between these two layers, no choroidal damage, and relatively little disruption of the inner retina. The typical argon lesion evidenced cellular damage from the RPE through all retinal layers. Leukocytes in the choroid contained "holes" or vacuoles not seen in YAG lesions. Both the uniformly pulsed YAG laser burst and argon laser produced effects consistent with a thermal process. Some differences between argon and YAG burst were observed. The results suggest that there may be a clinical potential for the 532-nm burst YAG in treating retinopathies.

Circulating C-peptide and diabetic retinopathy.

Basal serum C-peptide concentrations were determined in a series of adult males referred to a diabetic retinopathy clinic. Degree of retinopathy of the most affected eye of each subject was classified using stereoscopic fundus photographs and fluorescein angiograms. A positive correlation was found between low C-peptide concentration (3.0 +/- 2.1 ng/ml) and proliferative or pre-proliferative diabetic retinopathy. A significantly higher (p less than 0.01) C-peptide level was found in subjects with non-proliferative diabetic retinopathy (6.0 +/- 3.7 ng/ml). Determination of fasting C-peptide levels after the first five-year period of insulin-dependent diabetes appears to be useful as a predictor of risk for proliferative disease.

Corneal sulfate incorporation during fasting in rats.

Fasting is known to decrease sulfate incorporation as well as other growth functions in cartilage. The present study compared corneal sulfation in vivo and in vitro, with sulfation in cartilage of rats undergoing total food deprivation for 48 hours and refeeding for periods up to 28 days. Sulfate incorporation by cartilage decreased both in vivo and in vitro during the fast and recovered to normal values by 7 days of refeeding. Corneal sulfation increased in vivo during the fast. After 7 days of refeeding corneal sulfation in vivo dropped below the control value and remained below the control level. At later recovery periods corneal sulfation in vivo was normal. Corneal sulfation in vitro decreased during the fast. Normal cartilage showed a decrease in sulfate incorporation in vivo and in vitro with increasing age. Corneal sulfation in vitro followed this pattern, but corneal sulfation in vivo did not. We conclude that the effect of fasting on sulfate metabolism of corneal stroma is qualitatively different from that of cartilage.

Evaluation of visual acuity during laser photoradiation therapy of cancer.

Visual function for ten patients undergoing HPD-PRT was tested using 1) the Graham Field Eye Chart for distance vision, 2) pseudo-isochromatic plates for color vision, and 3) Amsler grid for changes in macular function. Whereas some increases and decreases in ocular function were observed, no clear patterns or changes of significance were observed.

Retinal cartography.

This paper analyses retinal cartography in terms of its reflection of anatomic data and its relation to several forms of geographic methods of map-making. It shows that the distances between anatomic landmarks of the eye are reasonably similar to the relative distances on the retinal drawing chart currently used. Two forms of geographic cartography--azimuth equidistant and orthographic--are described and compared with retinal cartography. The retinal drawing chart currently used most closely approximates an azimuth equidistant projection, which suffers from circumferential distortion, a fact that retinal surgeons must keep in mind. It is therefore recommended that the chart be modified to have equally spaced concentric circles and clearer identification of the ora serrata; the present accurate marking of anatomic landmarks, such as the equator and the posterior border of the ciliary body, should be preserved.