Peripheral retinal evaluation comparing fundus photographs with fluorescein angiograms in patients with diabetes mellitus.

PURPOSE: To evaluate peripheral nonproliferative retinopathy by comparing fundus photograph changes with angiographic findings in type 1 diabetic patients with a long duration of diabetes. METHODS: Thirty-eight patients with type 1 diabetes, without proliferative retinopathy and with at least 30 years of diabetes duration, were selected to be examined with fundus photography and fluorescein angiography. Two levels of retinopathy degree were identified. In fundus photographs, level 1 represented eyes with no or mild peripheral background retinopathy (i.e., five or fewer pinpoint hemorrhages or microaneurysms), and level 2, peripheral moderate retinopathy (i.e., dot-and-blot hemorrhages or intraretinal microvascular abnormalities or cotton-wool spots). In the angiograms, level 1 represented a nearly normal vascular pattern with occasional microaneurysms and level 2 comprised morphologic signs of abnormal circulation such as dilated capillaries, arteriolar abnormalities, intraretinal microvascular abnormalities, and capillary loss of 3 or more disk diameters from the center of the macula. The angiograms and fundus photographs were graded separately and the results of the grading were compared. RESULTS: The peripheral parts of the retina could be visualized with a high photographic quality on both fundus photographs and angiograms in 66 eyes. On fundus photographs, both graders found level 1 retinopathy in 47 of 66 eyes and level 2 retinopathy in 13 of 66 eyes. On angiograms, both graders found level 1 retinopathy in 46 of 66 eyes, whereas level 2 retinopathy was seen in 16 of 66 eyes. In most eyes with no or mild retinopathy, the angiograms were interpreted as nearly normal (41 of 47), and in most eyes with moderate retinopathy, they were interpreted as abnormal (10 of 13). CONCLUSION: The degree of peripheral diabetic retinal changes based on grading of fundus photographs was comparable to that based on angiograms in 51 of 66 (77%) eyes.

Fluorescein angiography versus ERG for predicting the prognosis in central retinal vein occlusion.

PURPOSE: It is not easy to predict which patients with a central retinal vein occlusion will develop rubeosis and which will not. We have compared two methods for doing so, fluorescein angiography and full-field electroretinogram (ERG). Our aim was to improve our possibilities for predicting rubeosis in patients with central vein occlusion. METHODS: 32 patients with a central retinal vein occlusion with a duration of less than 14 days were included in the study. Fluorescein angiography and ERG were performed in all patients. The fluorescein angiograms were studied by two independent examiners in a masked mode. The patients were then followed for at least one year. RESULTS: Development of rubeosis in patients with central retinal vein occlusion could be predicted by fluorescein angiography in 82% of the patients and with ERG in 94% of the patients. The non-ischemic central retinal vein occlusions were identified in 62% by fluorescein angiography and in 100% with ERG. Fluorescein angiography misjudged 9 patients 28%, whereas ERG only misjudged 1 patient, 3%. CONCLUSION: ERG seems to be a better method for predicting the prognosis in central retinal vein occlusion than fluorescein angiography.

The importance of early diagnosis of treatable diabetic retinopathy for the four-year visual outcome in older-onset diabetes mellitus.

The four-year visual outcome was retrospectively studied in patients with older-onset diabetes mellitus and diabetic retinopathy in need of laser treatment. Visual acuity in 53 patients examined by ophthalmologists who referred the patients for an evaluation of retinopathy before laser treatment, was compared to that of 47 patients examined by ophthalmologists who also performed the photocoagulation. The number of eyes that became blind (visual acuity < or = 6/60) during the four-year period was higher (23/90 vs 9/91; p < 0.01) among referred patients, whereas the number of retinal examinations per patient during the three-year period prior to laser treatment did not differ between the two groups. Among referred patients, 13% had not been ophthalmologically examined before the treatment-requiring retinopathy was found. Corresponding figure for those examined at the laser centre was 23%. Severe macular oedema in regularly examined patients was more common among referred patients (9/30 vs 1/32; p < 0.01). The results indicate that screening for diabetic retinopathy in older-onset diabetes was not performed satisfactorily. In addition, laser treatment was delayed in older-onset diabetic patients controlled by ophthalmologists who referred patients for photocoagulation, resulting in an increased incidence of legally blind eyes. The study also stresses the importance of carrying out knowledge of when and how to diagnose early sight-threatening diabetic retinopathy to ophthalmologists referring patients for laser treatment.

Structure elucidation of two tryptophan-derived, high affinity Ah receptor ligands.

BACKGROUND: Environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other structurally related 'environmental hormones', exert their harmful biological effects through the Ah receptor signaling pathway. Several naturally occurring substances also bind to this receptor, but its natural role is still obscure. Tryptophan derivatives of the indolo[3,2-b]carbazole type, earlier suggested by us to be endogenous ligands for the receptor, should be a powerful tool in understanding receptor function. We therefore set out to determine their identity. RESULTS: The two tryptophan-derived Ah receptor ligands have been chemically analyzed and characterized by means of mass spectrometry, 1H NMR and 13C NMR. UV, infra-red and fluorescence spectra were also recorded. All data are in accordance with the two compounds being closely related indolo[3,2-b]carbazole derivatives. Evidence is presented that compound A (MW = 312) is the symmetrical 6,12-diformylindolo[3,2-b]carbazole, and compound B (MW = 284) is the monosubstituted 6-formylindolo[3,2-b]carbazole. CONCLUSIONS: The elucidation of the structures of the two high affinity Ah receptor ligands 6,12-diformylindolo[3,2-b]carbazole and 6-formylindolo[3,2-b]carbazole provides the necessary basis for further mechanistic studies of this important group of compounds, and will help in determining the natural role of the Ah receptor.

Mutagenicity of tryptophan photoproducts in the Ames Salmonella assay.

During the photolysis of tryptophan a large number of products is formed. In this study, aqueous solutions of tryptophan were irradiated by ultraviolet light during 5, 20 or 40 h. Each of the irradiated batches was divided into two aliquots, which were freeze-dried or extracted with chloroform. For each batch the latter extract was subsequently divided into a purified chloroform extract and a methanol extract. Aliquots of the purified chloroform extracts were fractionated and pooled, peakwise, into seven fractions. A recombined sample was also constructed. All extracts and samples were tested for mutagenicity using the standard Ames Salmonella assay. The results indicate an exposure time dependent increase in mutagenicity of the extracts, as seen with tester strain TA100 both with and without metabolic activation. The mutagenicity of the freeze-dried extracts well approximated the mutagenicity of the chloroform extracts, indicating that most mutagenicity can be extracted with chloroform. With the fractions the highest mutagenic responses were seen in the late, i.e., less lipophilic fractions. This response pattern seen in TA98 and TA100, mainly with S9 activation, was in contrast to the response of TA102 without S9, which was highest to the more lipophilic fractions. On a fraction level, no general exposure dependent increase of mutagenicity was observed. The results also show that photooxidation of tryptophan gives rise to a different spectrum of products compared to pyrolysis. Both processes result in compounds with strong biological effects. Photooxidation results in compounds with low genotoxicity and high Ah receptor affinity while pyrolysis generates compounds with high genotoxicity and low or no Ah receptor affinity.

Growth hormone levels in the basal state and after thyrotropin-releasing hormone stimulation in young type 1 (insulin-dependent) diabetic patients with severe retinopathy.

Sixteen young patients with type 1 diabetes mellitus and rapidly progressive severe retinopathy were examined regarding serum levels of growth hormone before and after the i.v. administration of 200 micrograms thyrotropin-releasing hormone (TRH). Serum IGF I, HbA1c, blood pressure, urinary albumin, and serum creatinine levels were also measured. The control group consisted of type 1 diabetic patients matched for age, duration of diabetes and metabolic control with no or minimal background retinopathy. The results show that basal growth hormone levels were above normal in both groups, and that there was a paradoxical increment in growth hormone levels after TRH stimulation (p < 0.05) in patients with severe retinopathy, but the values did not differ from patients with background retinopathy. IGD I levels were normal in all patients but one, and no differences were seen between the two groups. HbA1c, serum creatine, blood pressure, and urinary albumin levels were similar in the groups but patients with severe retinopathy were treated with more insulin (p < 0.001). Thus, neither abnormal growth hormone levels, nor IGF I, seems to be associated with the development of severe retinopathy in young type 1 diabetic patients.

Optic disc swelling in an insulin-dependent diabetic. A result of drastic improvement of glucose control?

Rapid improvement of glucose control in diabetics may cause a transient progression of ischemic retinopathy. We report a transient bilateral acute asymptomatic optic disc swelling associated with rapid improvement of metabolic control in a male Type I diabetic. It is d, suggested that the optic disc swelling could be caused n of by a rapid near-normal normalization of the blood glucose.

Retinopathy and nephropathy in insulin-dependent diabetics: an inconsistent relationship?

The association between retinopathy and nephropathy was investigated in a retrospective study of 52 insulin-dependent diabetics with preproliferative or proliferative retinopathy and in 48 patients without or with background retinopathy. The duration of diabetes was 23.2 +/- 1.0 years (mean +/- SEM) and 22.0 +/- 1.2 years in the two groups. Patients in the retinopathy group showed a higher frequency of detectable nephropathy and were more often treated with antihypertensive drugs. However, a high proportion (35%) of patients with proliferative retinopathy did not show any detectable signs of nephropathy. Furthermore, nephropathy did not seem to develop in patients with retinopathy during an observation period of up to 9 years. The data suggest that the factors underlying the development of retinal and renal microangiopathy might be of different origin.