Peroxidase permeability of the cryogenic chorioretinal adhesion.

Under normal conditions the retinal pigment epithelium does not permit passage of peroxidase tracers. Photocoagulation disrupts this barrier. Rhesus monkeys which received transconjunctival cryotheropy showed a similar disruption, with leakage of horseradish peroxidase into the retina. This leakage persisted for the 6-month duration of the experiment. One month after treatment, a firm chorioretinal adhesion was present, characterized by gliosis, adherent junctions, and cellular interdigitation. The anatomic features of the cryogenic chorioretinal adhesion were similar to those previously described in human eyes.

A quantitative system to evaluate diabetic retinopathy from fundus photographs.

PURPOSE: To evaluate a quantitative system to measure the early lesions of diabetic retinopathy seen in stereoscopic fundus photographs. METHODS: Using a quantitative classification system, photographs of 4657 eyes (7 stereo pairs of 35-mm slides per eye) were scored for 16 diabetic lesions. A single severity level (identical to the ETDRS Interim Scale) was calculated for each eye. The reliability of this technique, and its reproducibility by independent examiners, was evaluated for individual lesions and severity levels using percent agreement, kappa, and weighted kappa statistics. RESULTS: This quantitative technique demonstrated an "almost perfect" agreement (weighted kappa > or = 0.810) on all but one lesion by independent observers. For the severity levels, there was a 95.7% perfect agreement (kappa = 0.9428). The reproducibility of agreement over time was "almost perfect" on all but four lesions; with 88% perfect agreement (kappa = 0.8394) for severity levels. CONCLUSIONS: When used to evaluate the early lesions of diabetic retinopathy, the Vanderbilt Classification System is highly reliable between graders and over time. This system can gather quantitative data and evaluate incremental changes in an accurate, reproducible manner.

An enzyme histochemical analysis of human subretinal fluid.

During rhegmatogenous retinal detachment, two major phagocytic cell populations can be identified in the subretinal fluid. Routine light and electron microscopic studies may be inadequate to assess quantitatively the free-floating retinal pigment epithelial cells and the macrophagic retinal pigment-laden cells. Enzyme histochemical staining permits a simple, rapid, reproducible method of identifying each cell type. This cytologic biochemical differentiation is an important tool for reexamination of the theories associated with subretinal fluid cell activity.

Ischemic optic neuropathy in migraine.

Two patients with histories of migraine had ischemic optic neuropathy develop during an episode of migraine. Clinical and radiologic studies excluded other causes of visual loss. Fluorescein angiography confirmed as ischemic process involving the optic dis. In both cases, visual loss was permanent. No further visual disturbance has occurred in either patient during a two-year period of follow-up while taking oral doses of propranolol hydrochloride.

Retinal vascular abnormalities in patients with coarctation of the aorta.

Pulsatile three-dimensional retinal arteriolar tortuosity has been previously reported in about 50% of patients with coarctation of the aorta. In a contemporary series of 20 patients with coarctation of the aorta, none exhibited this characteristic retinal vascular abnormality. Our findings suggest that the retinal vascular abnormalities in patients with coarctation of the aorta represent secondary hemodynamic changes. The prevalence of these abnormalities may be decreasing because of earlier surgical repair of coarctation.

Human biochemical components in retinoschisis and detachment.

Degenerative retinoschisis and rhegmatogenous retinal detachment are disorders that originate in the peripheral part of the retina. Both of these disorders are associated with biochemical processes that result in the finding of metabolic products within fluid-filled spaces. An attempt at biochemical differentiation of these two retinal disorders is described. Cholesterol, phospholipids, and proteins were present in the fluid samples, but low-density lipoproteins were not found. It is suggested that the cholesterol-to-phospholipid ratio may reflect the degree of retinal cellular destruction.

Hereditary sclerocornea.

Sclerocornea is a primary anomaly in which scleralization of a peripheral part of the cornea, or the entire corneal tissue, occurs. In the peripheral type of sclerocornea, the affected area is vascularized with regular arcades of superficial scleral vessels. In total sclerocornea, the entire cornea is opaque and vascularized. To our knowledge, 97 cases of all types of sclerocornea have been reported in the world literature, either as a primary anomaly or in association with cornea plana. Peripheral sclerocornea in association with cornea plana was found in nine members of one family, in four of five generations studied. To our knowledge, this is the largest pedigree of hereditary peripheral sclerocornea identified. Our pedigree suggests the autosomal-dominant transmission of this entity but doesn't rule out phenocopies or other modes of inheritance in other cases of sclerocornea. Chromosomal analyses of representative family members revealed normal karyotypes.

The insulin concentration in human ocular fluids.

We measured immunoreactive insulin concentrations in ocular fluids and serum of 19 patients. In rhegmatogenous retinal detachment patients without diabetes mellitus, the serum insulin level was 7 +/- 2 (SE) microunits/ml and the subretinal fluid insulin levels were mostly undetectable. By contrast, in rhegmatogenous retinal detachment patients with diabetes mellitus, serum insulin was 35 +/- 5 microunits/ml and the subretinal fluid always contained low but detectable amojnts of insulin. The data may suggest a small leak of insulin into the subretinal fluid of rhegmatogenous retinal detachment patients with diabetic retinopathy. In vitrectomy patients with diabetes mellitus there was no insulin in the vitreous in eight out of nine cases.

The topographic distribution of the first sites of diabetic retinal neovascularization.

PURPOSE: To examine the topographic distribution of the origin of diabetic retinal neovascularization. METHODS: The eyes of 3,121 patients with background diabetic retinopathy were investigated. These patients were volunteers in systemic medical therapy experiments. Color stereo photographs were obtained annually. The first retinal neovascularization sites were identified and the distances from the optic nerve measured. RESULTS: In 1 year, neovascularization originated in 282 eyes. The superotemporal quadrant, at 6 mm from the optic disk, was the most frequent initial site. CONCLUSIONS: The first retinal neovascularization sites cluster around specific anatomic foci. This information should influence retinopathy monitoring protocols.

Proliferative diabetic retinopathy in patients with defects of platelet function.

A 71-year-old woman had von Willebrand's disease, an inheritable abnormality of platelet activity, and developed diabetic retinal neovascularization. A 59-year-old man had a myeoloproliferative disorder with thrombocythemia but may have had retinal changes before the development of his platelet dysfunction. The occurrence of diabetic proliferative retinopathy in patients with reduced platelet activity suggests that platelet induced microcirculatory abnormalities may not be required for neovascularization.

Electron microscopy study of cryogenic chorioretinal adhesions.

By electron microscopy, the cryogenic chorioretinal adhesions in eight-day-old lesions from human eyes lacked anatomic adhesion between retina and choroid. In eight-month-old lesions, the neurosensory retina adhered to the retinal pigemtn epithelial layer by both desmosomal attachments and villous interdigitation.

Serum angiotensin converting enzyme in diabetic patients.

Serum angiotensin converting enzyme (ACE) levels are higher in patients with diabetes mellitus than in many others. Techniques are available to grade different degrees of diabetic retinopathy, which can demonstrate a relationship between ACE and diabetic retinopathy. In this study, patients with diabetic retinopathy had higher serum ACE levels (6.3 +/- 0.2) than nondiabetic patients (4.3 +/- 0.5) (p < 0.001). In addition, the mean serum ACE level in diabetic patients with nonproliferative retinopathy (5.55 +/- 0.4) was less than that in diabetic patients with proliferative retinopathy (6.63 +/- 0.25) (p = 0.02). Due to the variability in individual serum ACE levels and the frequent use of ACE inhibitors by hypertensive diabetics, these techniques are not suitable for retinopathy screening programs. However, the graded relationship demonstrated by these data may have relevance for the pathophysiology of diabetic retinopathy.

The decreasing incidence and severity of retinopathy of prematurity.

PURPOSE: We sought to determine whether the incidence of retinopathy of prematurity (ROP) at our institution has changed since the Cryo-ROP recruitment period 10 years ago. METHODS: We determined the incidences of threshold ROP, prethreshold ROP, less-than-prethreshold ROP, and no disease for each of 3 birth weight classes (<750 g, 750 to 999 g, and 1000 to 1250 g) of infants born between July 1, 1995, and June 30, 1996, and cared for in the Vanderbilt Neonatal Intensive Care Unit. We then compared these with the rates from our institution during the Cryo-ROP study recruitment period (January 1, 1986, to November 30, 1987). RESULTS: The current incidence and severity of ROP have decreased substantially overall and for each weight group compared with the 1986-87 incidence (P < .001, Cochran-Mantel-Haenszel test). The incidence of "any ROP" decreased by 27% for infants with birth weights less than 750 g, by 51% for infants 750 to 999 g, and by 71% for infants 1000 to 1250 g. The incidence of "prethreshold or greater ROP" decreased by 70% for the 750 to 999 g and 77% for the 1000 to 1250 g weight groups. Although the decrease in "prethreshold or greater ROP" was not as dramatic (25%) for the infants less than 750 g, only 1 infant (10%) progressed to threshold disease in this group, whereas 7 (47%) did in 1986-87. The incidence of threshold ROP decreased by 84% for infants less than 750 g and by 66% for infants 750 to 999 g. No infant with birthweight greater than 999 g progressed to threshold ROP. CONCLUSIONS: The incidence of all levels of ROP has decreased substantially for all infants with birth weights less than 1251 g at Vanderbilt University Medical Center during the past decade. Putative factors responsible for this decrease may include surfactant use, continuous pulse oximetry, aggressive use of antenatal steroids, and improved neonatal nutritional support.

The natural history of the first clinically visible features of diabetic retinopathy.

Microaneurysms are the first features of human diabetic retinopathy that can be detected with common clinical techniques. These are found, most often, in photographic field 2 (that is, an area occupying 30 degrees of the ocular fundus centered on the middle of the macula). After the first microaneurysms develop, there will be a tendency for more to appear; however, over time many of the original microaneurysms will become no longer visible with clinical techniques, while other, newer, microaneurysms mature. After the onset of microaneurysms, several years may pass before any other diabetic retinopathic lesions develop. Lesions other than microaneurysms were uncommon in this study; the following is a list in decreasing frequency: retinal hemorrhages, soft exudates, IRMA, hard exudates, and venous beading. During the 4 years of this study, there were no other diabetic retinopathic lesions detected. The duration of insulin-dependent diabetes mellitus was related to the rate of change in microaneurysm counts. The age and sex of patients did not affect this rate of change. The accuracy of metabolic control, as determined by glycosylated hemoglobin levels, may influence this rate of change; however, this was detected only at the extremes of measurement in this study. The equipment available to most ophthalmologists can detect the earliest clinical aspects of diabetic retinopathy. These features can be quantified in a reproducible manner with standardized photographic techniques to permit satisfactory data analysis.

The Vanderbilt Classification System in the evaluation of diabetic retinopathy patients treated with Alredase.

BACKGROUND: The Vanderbilt Classification System is a quantitative method of measuring features detected in diabetic retinopathy photographs. It does not require comparisons to preexisting standard photographs. This is the first report of the application of this system to a large-scale, multiple-medical-center drug trial. METHODS: This was a prospective, randomized, double-masked, placebo-controlled study that involved 74 medical centers. There were 3,679 out-patients followed for more that 4 years, with some observed for over 9 years. The Vanderbilt Classification System generated patient data for the Early Treatment Diabetic Retinopathy Study (ETDRS) and the Diabetes Control and Complication Trial (DCCT) scales. The deterioration rate was one variable used to assess drug effect. A comprehensive Quality Assurance Program evaluated intergrader and intragrader reliability. RESULTS: Target values for reliability and reproducibility were met or exceeded on all measures of agreement between photo readers and over time. Kappa statistics were 0.610 or greater, with most weighted kappa values greater than 0.810. This represents "almost perfect agreement" and compares favorably with previous reports from the ETDRS and DCCT. CONCLUSION: Diabetic retinopathy can be evaluated in a reliable and reproducible manner with the VCS. The VCS is unique in that it produces a quantitative analysis of retinal lesions. Subtle variations that might be influenced by systemic medications can be measured accurately with this technique.