Automated grading of venous beading.

The degree of venous beading in ocular fundus images has been shown to be a more powerful predictor of conversion to proliferative diabetic retinopathy than any other type of retinal abnormality. Further, the degree of venous beading has been shown to be well correlated with disease progression. An algorithm for automated grading of venous beading in digitized ocular fundus images is described. Thresholding is used to extract a rough silhouette of the vein. Morphological closing is used to fill any holes in the silhouette arising from either the central light reflex or noise. The silhouette is then "thinned" to find vein centerlines. Each centerline is partitioned into fixed-length segments of 32 pixels. Vein diameters are measured as a function of distance along each segment with the aid of the local centerline orientations. The resulting diameter data are then interpolated and resampled to generate diameter data at constant sampling intervals. A fast Fourier transform is performed on the resulting data to determine the magnitude spectrum of vein segment diameter. A venous beading index is calculated from the distribution of vein diameter frequency components. Performance of the new algorithm is compared to the currently accepted clinical practice of manual grading in a pilot clinical study of 51 subjects. The algorithm is seen to perform well.

Use of ophthalmologic services by diabetic patients in Nova Scotia.

To evaluate the possible public health consequences of diabetic retinopathy in Nova Scotia, we investigated the number and frequency of ophthalmologic examinations in patients with diabetes mellitus. A total of 36,683 people (4.2%) were identified from the administrative database of the provincial health department as having a diagnostic code of diabetes during the period March 1987 to February 1990. All billings by ophthalmologists for these patients during the same period were then identified. Of the 36,129 patients aged 10 years or more, 17,518 (48.5%) had seen an ophthalmologist at least once during the study period, and 5218 (14.4%) had seen an ophthalmologist approximately annually. Increased age and being female were associated in univariate logistic regression analysis with higher use of ophthalmologic services. The medical insurance system is free of direct costs to patients, and there are enough ophthalmologists to meet patient needs (4.35 per 100,000 population). The findings indicate that most diabetic patients in Nova Scotia are not seen at least once a year, as recommended by the Expert Committee of the Canadian Diabetes Advisory Board, despite ready availability of ophthalmologic care.

Automated detection and quantification of venous beading using Fourier analysis.

Venous beading associated with diabetic retinopathy is currently assessed by means of subjective comparison to standard photographs from the modified Airlie House classification scheme. We describe a computerized grading scheme for venous beading. The algorithm, based on Fourier analysis of vessel width measurements, generates a venous beading index (VBI) for digitized colour fundus photographs. Colour photographs of local vessel segments about 1200 microns in length were evaluated by experienced graders. A comparison between the VBI and subjective grading showed good agreement. The mean VBI values across the four levels of clinical grading were significantly different (p = 0.000). Multiple comparison testing indicated that the VBI was able to significantly differentiate between all four categories except the "questionable" (grade 1) category (p < 0.05). We also found that progression of venous beading can be followed with the VBI. The results indicate that further development of automated grading of venous beading is warranted.

Negative predictive value of a population-based preschool vision screening program.

BACKGROUND: The Enhanced Vision Screening Program is a population-based vision screening program that has, at present, examined 59,782 children. Its main goal is to detect amblyopia, strabismus, and high refractive errors. An average of 11,910 4 1/2- to 5 1/2-year-old children are screened yearly. The current study determines the negative predictive value of the screening program: For a subject having passed the vision screening test, what is the probability of not having amblyopia, strabismus, or high refractive errors? METHODS: Of the 11,734 subjects who passed the vision screening, 200 were randomly chosen to undergo a strictly defined gold standard examination by an orthoptist and an ophthalmologist. RESULTS: Of the 200 randomly chosen subjects, 157 underwent the gold standard evaluation. The negative predictive value of the Enhanced Vision Screening Program was 97.6% for any potentially vision-threatening ocular condition. It was 98.7% if we considered only the visually significant ocular problems that the test was designed to detect. CONCLUSION: Because the negative predictive value of the Enhanced Vision Screening Program is not 100%, some children with amblyopia, strabismus, or refractive errors are missed. Occasionally, a rare, potentially vision-threatening condition may go undetected. Parents should be made aware of this when they receive the results of the vision screening.

Growth hormone suppression and nonproliferative diabetic retinopathy: a preliminary feasibility study.

We used the long acting somatostatin analogue SMS 201-995 in order to examine the feasibility and effect of medical suppression of growth hormone in nonproliferative diabetic retinopathy. Six insulin-dependent diabetic subjects with nonproliferative retinopathy were studied. After eight weeks of SMS 201-995 administration, 24-hour integrated plasma growth hormone concentrations had declined by 47.0 +/- 9.3% of pretreatment values (p less than 0.01), and insulin requirements fell from 40.7 +/- 6.7 units per day to 32.2 +/- 6.9 units per day (p less than 0.01). Plasma levels of somatomedin-C were low before SMS 201-995 (0.5 +/- 0.1 U/ml) and remained unchanged at eight weeks (0.6 +/- 0.1 U/ml; p = ns). During SMS 201-995 administration, best corrected visual acuity improved in both right eyes (53.8 +/- 2.57 to 59.8 +/- 0.7 letters, p less than 0.05) and left eyes (54.8 +/- 2.8 to 61.7 +/- 1.23 letters, p less than 0.03). Fluorescein angiography and stereo fundus photography demonstrated concurrent improvement in retinopathy level in only two subjects. Following cessation of SMS 201-995 treatment, visual acuity returned to pretreatment levels in both right eyes (54.5 +/- 2.4 letters, p = ns compared to baseline) and left eyes (55.8 +/- 2.6 letters, p = ns compared to baseline). These results demonstrate that growth hormone was only partially suppressed by SMS 201-995 in insulin-dependent diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Foscarnet therapy of cytomegalovirus retinitis in AIDS.

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in AIDS. Twenty patients were treated with a 21-day course of foscarnet therapy by continuous infusion. Response to therapy was good in eight (47%) of 17 evaluable patients; partial arrest of progression was observed in eight (47%); and no response was obtained in one (6%). Foscarnet therapy did not lead to suppression of urinary excretion of CMV in four of 12 patients who nonetheless had improvement in retinal lesions. Toxic effects, especially reversible renal failure, were common, with blood creatinine increase in 50% and dialysis in two patients. Renal toxicity occurred primarily during the third week of therapy. Anemia (hemoglobin less than 80 g/L) occurred in 10 patients after a mean of 14.5 +/- 5.1 days of therapy and required transfusion. Review of this study and of data from a previous case series, however, was inconclusive regarding the additional benefit of a third week of therapy. Maintenance therapy was given to seven patients. Four had recurrence of CMV retinitis at a mean interval of 62 +/- 52 days. Only one patient has maintained prolonged remission on maintenance (greater than 24 weeks). Toxicity on the maintenance protocol included anemia (two of seven patients) and increased creatinine blood levels (one of seven patients). Zidovudine therapy in six patients did not contribute to increased toxicity of induction or maintenance therapy. Drug levels during continuous infusion were stable for individual patients but showed wide inter-patient variability. Peak levels of post-maintenance infusion varied both within and between patients.

Pharmacological characterization of adrenal paraneurons: substance P and somatostatin as inhibitory modulators of the nicotinic response.

A pharmacological study was made of the effects of various muscarinic and nicotinic agonists and their antagonists on the release of [3H]noradrenaline ([3H]NA) from cultures of isolated bovine adrenal medullary cells. A study was also made of the effects of substance P and somatostatin on the release of [3H]NA evoked by nicotinic agonists. By 2 days in culture these adrenal 'paraneurons' had developed long varicose processes with growth cones and generally resembled noradrenergic neurons in culture. In the present study, adrenal paraneurons were incubated with [3H]NA which was taken up and stored in reserpine-sensitive sites. Exposure of the cultures to acetylcholine (ACh) resulted in release of [3H]NA into the external medium. High concentrations of K+ (56 mM) also evoked release of [3H]NA. The release of [3H]NA induced by ACh or K+ (56 mM) was Ca2+-dependent. Pharmacological studies with nicotinic (ACh, nicotine) and muscarinic (methacholine, pilocarpine) agonists and their antagonists (mecamylasmine, d-tubocurarine, hexamethonium; and atropine, scopolamine, respectively) showed that the adrenal paraneurons contained only nicotinic receptors. Substance P produced a dose-dependent inhibition of ACh (5 x 10(-5) M) stimulated [3H]NA release in the range of 10(-8) to 5 x 10(-5) M with an ID50 of 10(-6) M. A similar inhibition of NA release by substance P was obtained when nicotine (K X 10(-6) M) was used as the agonist, but not when K+ (50 MM) was used to depolarize the cells. Substance P (10-10) to 5 x 10(-5) M) by itself did not have a significant effect on the basal release rate of [3H]NA from these cells. Somatostatin at relatively high concentrations (10(-6)-10(-3) M; ID50 2 x 10(-5) M) inhibited the release induced by ACh, but not by K+ (56 mM). The present results provide the first direct evidence at a cellular level that substance P and somatostatin act as inhibitory modulators of the nicotinic ACh response, and support a role for these peptides as inhibitory neuromodulators at nicotinic receptor sites in the nervous system.