Lens-corrected visual field sensitivity and diabetes.

PURPOSE: To examine whether peripheral S-cone system and achromatic sensitivity was reduced in patients with diabetes compared to normal controls. METHODS: Perimetric measurements were obtained to study peripheral S-cone system and achromatic sensitivity in patients with diabetes and normal controls. Measures of individual lens absorption of short-wavelength light were used to correct visual field sensitivity values for attenuation of test light due to lens absorption. RESULTS: Both before and after correction for lens absorption of test spot light, peripheral field-averaged S-cone system and achromatic sensitivities were not significantly reduced among patients with diabetes compared to normals of the same age. However, localized sensitivity losses in the visual field were found in most patients with diabetes both before and after lens absorption correction, compared to age norms. The amount of localized loss (number of field locations with reduced sensitivity) was significantly correlated with the level of retinopathy. Statistical analysis showed that after the effects of age and duration were removed, field-averaged S-cone system sensitivity in patients with diabetes was also significantly reduced as a function of increasing severity of retinopathy. CONCLUSIONS: Patients with diabetes may have areas of reduced S-cone system sensitivity with development of diabetic retinopathy.

Lenses of diabetic patients "yellow" at an accelerated rate similar to older normals.

The authors used a psychophysical method to measure lens transmission of young, type I diabetic patients and normal controls. The results from normal controls agreed with previously published reports of decreasing lens transmission with age, and those from diabetic subjects suggested that lenses of young, type I diabetic patients age or "yellow" at an accelerated rate that was similar to that of normal controls over the age of 60 yr. The rate of accelerated lens density that occurs per year with the duration of diabetes is similar to the rate of accelerated lens density that occurs per year with patient age over 60 yr. A possible molecular explanation for the accelerated lens yellowing in both populations is discussed. Both diabetic individuals and the older normal populations have elevated plasma glucose levels and therefore may have accelerated glycosylation of lens proteins which causes increased lens yellowing.

Characterization of the electroretinographic scotopic B-wave amplitude in diabetic and normal subjects.

The intensity-response function of the scotopic b-wave of the electroretinogram may be a useful device for monitoring patients with retinal disease. Three models were evaluated that describe this function in 152 patients with diabetic retinopathy of varying severity and in 40 nondiabetic comparison subjects. The models considered were the Naka-Rushton equation fit to all 21 data points collected, the Naka-Rushton equation fit to the data points below the "second limb" of the function, and a log-linear fit only to data at the nine lowest intensities. In addition, the b-wave amplitude at each intensity tested was evaluated individually. Model parameters and amplitude measurements were compared with respect to (1) their ability to distinguish diabetic from nondiabetic subjects determined from the area under the receiver operating characteristic curve and (2) their correlation with retinopathic severity, graded in a standard fashion in fundus photographs. When all the parameters of each model were used in combination, there were no significant differences among the models with either evaluation criterion. Furthermore, b-wave amplitudes at midrange intensities (near -2.2 log cd-sec/m2) did approximately as well as any model.

Spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy (Boucher-Neuhäuser syndrome)

We describe two families (including one previously reported) in which cerebellar or spinocerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy result from abnormal function of an autosomal recessive gene. Review of the literature adds one other family with this disorder. These three examples confirm the existence of this traid as a specific, pleiotropic, single-gene syndrome. Careful ophthalmologic evaluation of patients with ataxia and hypogonadotropic hypogonadism may identify additional cases.

Brachydactyly-short stature-hypertension (Bilginturan) syndrome: report on two families.

We report on two families with autosomal dominant brachydactyly of hands and feet and hypertension. All affected members of the first family had proportionate short stature. However, the propositus and the affected relatives in the second family were only short compared to unaffected relatives. The hypertension was medically responsive in all cases. The propositus in the second family had poor compliance and a striking generalized vasculopathy. All patients were of normal intelligence and had a normal facial appearance. The brachydactyly-short stature-hypertension syndrome was first reported by Bilginturan et al. [1973] in a Turkish family and the families reported by us are Caucasian and Hispanic. The gene causing this condition in the original Turkish family was recently mapped to 12p. Our report expands our existing knowledge and the ethnic diversity of this syndrome.

Predicting progression to severe proliferative diabetic retinopathy.

The longer-term progression of retinopathy was observed in a previously described group of 85 diabetic patients enrolled in the Early Treatment Diabetic Retinopathy Study. The probability of progression to severe retinopathy was significantly greater for eyes with the following baseline characteristics: greater overall retinopathy severity, higher fluorescein leakage, higher capillary nonperfusion, and lower electroretinographic oscillatory potential amplitudes. The summed amplitudes of the oscillatory potentials, the overall severity of retinopathy, and the severity of fluorescein angiographic leakage were found to be independent predictors of progression to severe proliferative retinopathy in a regression model; capillary nonperfusion was not found to predict progression independently when fluorescein leakage was included in the model. Probability curves based on the regression model can be used to support clinical decisions concerning when to perform panretinal laser photocoagulation and how often to follow up patients with less than severe proliferative diabetic retinopathy.

Temporal aspects of the electroretinogram in diabetic retinopathy.

We measured the temporal aspects of several components of the electroretinogram in 72 patients with diabetes and 29 control subjects. The measurements consisted of the implicit times of the a wave and oscillatory potentials elicited by a bright-flash stimulus and the implicit time of the b wave in response to a 30-Hz flickering light. The a wave and first three oscillatory potential nodes were significantly delayed in the patients with diabetes compared with the controls; among the diabetics, a significant increase in the delay of the second and third nodes occurred as a function of increasing retinopathy severity. Similarly, the 30-Hz flicker implicit times (with and without a background light) were significantly delayed in patients with diabetes, and the magnitude of the delay increased with increasing retinopathy severity. The correlations of 30-Hz flicker implicit times with retinopathy severity were significant for retinopathy level graded in color fundus photographs as well as for retinal capillary nonperfusion and leakage graded in fluorescein angiograms. A comparison of 30-Hz flicker implicit times in 15 patients with one eye treated with panretinal laser photocoagulation and the other eye untreated (treatment was randomly assigned) showed a significant delay in the treated eyes compared with the untreated eyes (paired eye comparison). This suggests that panretinal laser photocoagulation induces a further delay in the b-wave implicit times of eyes treated for diabetic retinopathy.

Oscillatory potential amplitudes. Relation to severity of diabetic retinopathy.

The oscillatory potentials of the electroretinogram and other visual function tests were evaluated in a group of 174 diabetic and 54 control subjects. Retinopathy severity in diabetic patients was measured in color fundus photographs and fluorescein angiograms. The summed amplitudes of the oscillatory potentials were significantly lower in diabetic compared with control subjects, and the amplitudes decreased progressively as the retinopathy severity increased. Among diabetic patients, a significant correlation was found between the oscillatory potentials and the other visual function tests; lower amplitudes were associated with lower visual field and visual acuity scores and higher Farnsworth-Munsell 100-hue error scores. Stepwise regression analysis showed that the most important predictors of oscillatory potential amplitudes were retinopathy level, fluorescein leakage, and age; capillary nonperfusion did not add to the predictive power of the model when fluorescein leakage was included.

Butterfly-shaped macular dystrophy in four generations.

Four generations in a family were affected by butterfly-shaped macular dystrophy. Affected members ranged in age from 8 to 77 years. In addition to the primary features of autosomal dominant inheritance, bilateral symmetrical pigmented macular lesion, and a low electrooculographic light peak-dark trough ratio, we discovered additional progressive changes: peripapillary and parafoveal chorioretinal atrophy, enlarged blind spots, and paracentral scotomas with diminished visual acuity late. Because of the progressive change in the ophthalmologic appearance of the fundus, the diagnosis could easily be overlooked in advanced cases.

Retinal wrinkling and macular heterotopia in diabetic retinopathy.

Retinal wrinkling of the posterior pole was studied in 40 eyes from 31 patients with diabetic retinopathy. Vitreoretinal traction was thought to produce the wrinkling in 32 of the eyes, in 13 of which macular heterotopia also developed, presumably from the same tractional forces. Epiretinal membrane formation was the apparent causal factor producing retinal wrinkling in six eyes and postphotocoagulation chorioretinal scarring in two eyes, in none of which macular heterotopia developed. Retinal wrinkling alone was associated with only mild or no visual acuity loss. Macular heterotopia was associated with more severe loss of visual acuity and with other visual symptoms. Displacement of retinal vessels was an important clue to the diagnosis of macular heterotopia.

Macular heterotopia in proliferative diabetic retinopathy.

Macular heterotopia secondary to proliferative diabetic retinopathy has been previously reported in clinical cases. To our knowledge, we present the first clinicopathologic case of macular heterotopia in a young patient with proliferative diabetic retinopathy. The significant pathologic findings included dense fibrovascular tissue on the disc to correspond with nasal tractional retinal detachment, a superonasally displaced fovea, and an area of stripped and recoiled internal limiting membrane overlying a retinal fold. In addition, an area of reduplicated retinal pigment epithelium was noted corresponding to the clinically observed hyperpigmented area superior to the heterotopic fovea. Despite the pathologic changes, the patient maintained 20/40 visual acuity with the heterotopic fovea for several years. The findings are discussed in relation to previous clinical studies.

Electroretinographic oscillatory potentials predict progression of diabetic retinopathy. Preliminary report.

The oscillatory potential (OP) amplitudes of the electroretinogram (ERG) were determined in a group of 85 diabetic patients entering the Early Treatment Diabetic Retinopathy Study (ETDRS). The rate of progression among nonphotocoagulated eyes to the Diabetic Retinopathy Study high-risk characteristics (DRS-HRC) during a ten- to 40-month follow-up period was determined. Progression occurred in 19 of 85 eyes at risk. Those eyes with abnormal OP amplitudes (less than or equal to 75 microV) at study entry had a tenfold higher rate of progression to DRS-HRC than did eyes with normal amplitudes (greater than 75 microV). Although the level of retinopathic severity at study entry was a significant factor in the rate of subsequent progression, the amplitudes of the OPs remained a significant risk factor even after correcting the initial retinopathic level. The ERG seems to be a useful clinical tool in predicting the rate of progression of diabetic retinopathy. The reduction in OP amplitudes probably is a quantitative measure of the degree of overall inner layer retinal ischemia.

Autosomal dominant peripheral preretinal deposits.

Abnormal yellow-white peripheral preretinal deposits are described as an autosomal dominant disorder in ten members of a large pedigree spanning three generations. The absence of any other major vitreoretinal abnormalities or retinal function disorders suggests that this is a benign disease; the nature and origin of the preretinal deposits is obscure.

Urinary glucose testing inaccuracies among diabetic patients. Effect of acquired color vision deficiency caused by diabetic retinopathy.

The performance of two urinary glucose tests (Clinitest and Diastix) and several color vision and lightness discrimination tests was assessed in 43 diabetic patients and 43 age-matched controls. Most of the diabetics had proliferative diabetic retinopathy, with normal or mildly reduced visual acuity. The diabetics made significantly more errors on color interpretation of the urinary test results than did controls. The extent of errors for both diabetics and controls correlated with the severity of color vision deficiency but not with lightness discrimination deficiency. The diabetics' performance of the Clinitest test and, to a lesser extent, of the Diastix test was significantly better in bright light than in dimmer light. The type of color vision deficiency among most of the diabetics was characteristic of the acquired blue-yellow defect associated with diabetes mellitus. All of the color vision tests enabled identification of patients likely to make a large number of urine-testing errors with high sensitivity and fairly high specificity.

Choroidovitreal neovascular ingrowth after photocoagulation for proliferative diabetic retinopathy.

In eight patients with proliferative diabetic retinopathy treated with focal photocoagulation for preretinal new vessels, recurrent preretinal new-vessel systems supplied from the choroid developed. Subsequent treatment in most cases failed to produce permanent obliteration of the new-vessels networks.

Clinicopathologic correlations in diabetic retinopathy. II. Clinical and histologic appearances of retinal capillary microaneurysms.

One eye of a 21-year-old patient with proliferative diabetic retinopathy was available for clinicopathologic correlation. The fluorescent spots in a fluorescein angiogram were correlated with the changes in color fundus photographs and with the corresponding histologic findings in a trypsin digest preparation of the retina. A round, regular fluorescent spot was the most reliable diagnostic indicator of retinal capillary microaneurysms, although some microaneurysms appeared as irregular fluorescent spots, tiny fluorescent spots, or dark silhouettes with or without fluorescent halos. Very large fluorescent spots correlated with very large irregular pouches that may represent intraretinal neovascularization. Fluorescein angiography was considerably more sensitive than color fundus photography for the detection of retinal capillary microaneurysms.

Retinal ischemia in diabetic retinopathy.

Eight patients with proliferative diabetic retinopathy developed extensive retinal arteriolar and capillary obstruction. Ophthalmoscopy showed many white, thread-like retinal arterioles associated with capillary and venous dilatation. Widespread retinal arteriolar and capillary nonperfusion was demonstrated by fluorescein angiography. Ischemic maculopathy resulted in severe loss of visual acuity in some eyes. The severe degree of retinal ischemia was accompanied by optic disc pallor and neovascularization and a high incidence of rubeosis iridis with neovascular glaucoma. Patients with this variety of diabetic retinopathy have a poor prognosis of retaining useful vision.

Abnormalities of the foveal avascular zone in diabetic retinopathy.

The dimensions of the foveal avascular zone (FAZ) were measured in fluorescein angiograms from 36 diabetic patients and 20 nondiabetic controls. The median values for longest diameter, mean diameter, and circumference were significantly greater in the diabetic group than in the control group. Longest diameters greater than 1.0 mm were found almost exclusively in eyes with proliferative diabetic retinopathy. The FAZ dimensions were strongly positively correlated with the severity of capillary nonperfusion in the posterior retina, but not with fluorescein leakage. The presence of proliferative diabetic retinopathy was also strongly correlated with capillary nonperfusion. Retinal capillary occlusion as the cause of FAZ enlargement in diabetic retinopathy is supported by these findings.

Pars plana vitrectomy. Treatment for tractional macula detachment secondary to proliferative diabetic retinopathy.

Pars plana vitrectomies were performed on 43 eyes with traction macular detachment secondary to proliferative diabetic retinopathy. Anatomic success, as judged by reattachment of the macula, occurred 28 (65%) eyes. Improved visual acuity occurred in 11 (26%) eyes. Severe complications occurring after vitrectomy included moderate to severe rubeosis iridis diabetica (28%), neovascular glaucoma (16%), vitreous hemorrhage (49%), and phthisis bulbi (14%). Eyes that received scatter photocagulation therapy at some time prior to macular detachment had a substantially lower incidence of successful postoperative reattachment of the macula than eyes never treated with photocoagulation.

Association of hue discrimination loss and diabetic retinopathy.

The results of Farnsworth-Munsell 100-hue, visual acuity, and visual field testing were compared with the severity of retinopathy in a group of 90 diabetic patients. The patients showed significantly higher than expected Farnsworth-Munsell 100-hue scores, with a tritanlike axis, compared with published age norms for nondiabetic individuals. The magnitude of the acquired blue-yellow hue discrimination defect correlated significantly and to a similar extent with both the severity of overall diabetic retinopathy and the severity of macular edema and hard exudate formation. Visual acuity loss correlated somewhat more significantly with macular edema than with overall retinopathy, whereas the converse was true for visual fields. For all visual function tests, the correlations were more significant for fluorescein leakage in the macula than for capillary nonperfusion in the macula. Abnormal hue discrimination was found in 65% (32/49) of eyes with proliferative diabetic retinopathy, suggesting a potential role for this test in screening for proliferative diabetic retinopathy in primary care facilities. Also, because the ability of diabetic patients with color vision deficiency to perform color-dependent tests for urinary and blood glucose may be impaired, such patients should be made aware of this potential problem.