Anterior clinoid mucocele masquerading as retrobulbar neuritis.

Mucoceles arising from the anterior clinoid is rare. Although intrinsically benign, mucoceles in the sphenoid sinus (anterior clinoid variant) can lead to complications due to their proximity to other structures. We present a case of a young man whose visual complaints were typical for retrobulbar optic neuritis. Results of radiologic tests for diagnosis led us to the early detection of a surgically treatable condition, a sphenoid sinus mucocele (anterior clinoid variant). Early surgery was helpful in ameliorating the symptoms, leading to full recovery of visual function. The clinician should be aware of this rare entity with its presentation in a wide variety of signs and symptoms.

Cardiovascular autonomic neuropathy and proliferative diabetic retinopathy.

PURPOSE: To determine prospectively whether cardiovascular autonomic neuropathy is a risk factor for proliferative diabetic retinopathy. METHODS: A five-year follow-up study of 88 diabetic persons was performed at a center providing primary and specialized care for diabetes. Participants were white, insulin-dependent patients with diabetes of 15 to 21 years' duration. The primary end point was the presence of proliferative diabetic retinopathy, seen either on fundus photography or ophthalmologic examination. Cardiovascular autonomic neuropathy was measured at baseline by using a standard protocol. RESULTS: Fourteen patients developed proliferative diabetic retinopathy during follow-up. One measure of cardiovascular autonomic neuropathy, the 30:15 ratio, the heart rate variation at the 30th beat compared with that at the 15th beat, was lower among patients with proliferative diabetic retinopathy (P = .0049) The risk of proliferative diabetic retinopathy in patients with an abnormal cardiovascular autonomic neuropathy index was 2.59, although the estimate was not statistically significant because of the small number of patients who developed proliferative diabetic retinopathy. CONCLUSIONS: This study provides prospective evidence that cardiovascular autonomic neuropathy is associated with proliferative diabetic retinopathy. In addition to ocular determinants of proliferative diabetic retinopathy, systemic risk factors also should be considered when examining patients with diabetes mellitus.

Psychosocial adjustment to advanced proliferative diabetic retinopathy.

OBJECTIVE: To identify the major problems with adjustment to the advanced stages of proliferative diabetic retinopathy and to examine the relationship between adjustment and visual acuity. RESEARCH DESIGN AND METHODS: A cross-sectional descriptive cohort study was conducted at the referral-based eye unit at Joslin Diabetes Center in Boston, Massachusetts. We studied 47 adults with IDDM and advanced proliferative diabetic retinopathy. Thirty reported recent visual loss, and 17 had more stable vision. RESULTS: Psychosocial Adjustment to Illness Scale scores were significantly elevated relative to a normative diabetic sample (t = 2.94, P < 0.01). Our proliferative diabetic retinopathy sample reported the most difficulties in the domain of health-care orientation. No significant differences were observed in adjustment scores between those with recent partial visual loss and those with more stable vision. However, visual acuity in the best eye correlated significantly with the proliferative diabetic retinopathy sample's total adjustment score (r = -0.34, P = 0.02) and with 4 of 7 adjustment subscales. CONCLUSIONS: These results suggest that advanced proliferative diabetic retinopathy may be associated with particular difficulties in adjustment that are more related to best visual acuity than to recent visual loss. Relatively mild visual impairment may have significant psychosocial impact.

Different determinants of neovascularization on the optic disc and on the retina in patients with severe nonproliferative diabetic retinopathy.

Almost all patients with type I and many with type II diabetes develop proliferative retinopathy. This entity consists of two components: new blood vessels on the optic disc (NVD), which frequently lead to visual loss, and new blood vessels elsewhere on the retina (NVE), which do not pose such a serious threat to vision. This study examined determinants of neovascularization specifically on the optic disc in eyes with severe nonproliferative retinopathy. The study eyes were under surveillance as the untreated control eyes of participants in the Diabetic Retinopathy Study. During the 5-year follow-up period, NVE developed in almost all of the eyes, whereas the cumulative incidence of NVD in these same eyes was 64% and varied according to several factors. The risk of NVD in a study eye was increased if the contralateral treated eye had NVD rather than NVE or severe nonproliferative retinopathy (odds ratio [OR], 6.1; P < .0001). It was also increased if the study eye had, at the baseline examination, soft exudates and intraretinal microvascular abnormalities (OR, 5.7; P = .002) or soft exudates alone (OR, 4.0; P = .04). Nephropathy and poor glycemic control were each associated with a two-fold increase in risk but neither was statistically significant. Eyes of individuals over 40 years of age were protected from the development of NVD (OR, 0.5; P < .05). The findings of this study support the hypothesis that, in patients with diabetes, the development of NVD is determined by different factors than the development of NVE.

Risk of early-onset proliferative retinopathy in IDDM is closely related to cardiovascular autonomic neuropathy.

Determinants of proliferative diabetic retinopathy (PDR) that occur during the 2nd decade of insulin-dependent diabetes mellitus (IDDM) (early-onset PDR) were investigated in a nested case-control study. From an inception cohort of patients with juvenile-onset IDDM that now has 15-21 yr diabetes duration, the patients with PDR (cases, n = 74) were selected for study along with a random sample of the patients in the cohort without PDR (control subjects, n = 88). The risk of PDR was associated with poor glycemic control during the first 12 yr of diabetes. Relative to patients in the first quartile of the index of hyperglycemia, those in higher quartiles and nonattenders had a four- to fivefold risk of developing PDR. A striking relationship with cardiovascular autonomic neuropathy (CAN) was found. Relative to patients without CAN, patients with significant and mild CAN had odds ratios of 77.5 and 34.6, respectively. Patients with albumin excretion rates greater than 30 micrograms/min had moderately increased risk of PDR (ranging from 4-fold for microalbuminuria to 7-fold for proteinuria). In contrast, patients with impaired renal function had an extremely high risk of PDR. All 20 of these patients were cases, therefore the odds ratio was infinite. All three factors (poor glycemic control, CAN, and various stages of nephropathy) were associated with PDR in multiple logistic regression analysis. However, in models including glycemic control, the association between microalbuminuria or proteinuria and PDR was weakened. In conclusion, our findings are consistent with a hypothesis that the level of glycemia is a primary determinant of early-onset PDR.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk for cardiovascular autonomic neuropathy is associated with the HLA-DR3/4 phenotype in type I diabetes mellitus.

OBJECTIVE: To identify risk factors for the development of cardiovascular autonomic neuropathy in patients with juvenile-onset type I diabetes mellitus. DESIGN: Cross-sectional examination of an inception cohort 15 to 21 years after the onset of diabetes. SETTING: Outpatient diabetes clinic. PATIENTS: Seventy-nine patients with type I diabetes who experienced onset of disease before 21 years of age and who were followed for 15 to 21 years. MEASUREMENTS: Autonomic nerve function was evaluated in all patients using deep breathing and tilt tests. On the basis of these tests, an index of cardiovascular autonomic neuropathy was derived and patients were classified as having intact, mildly impaired, or significantly impaired autonomic function. RESULTS: The group with significantly impaired function had a higher mean hemoglobin A1 at the time of examination than the group without impairment, yet the groups did not differ regarding glycemic control during the first decade of diabetes. The HLA-DR3/4 phenotype was present in more than 50% of the patients with significant autonomic dysfunction and conferred relative odds of 6.2 (95% CI, 1.7 to 23.3) for the development of autonomic neuropathy when compared with other HLA-DR phenotypes. Sex, percent ideal body weight, and smoking did not have a statistically significant effect on the development of autonomic neuropathy. CONCLUSIONS: The development of cardiovascular autonomic neuropathy in type I diabetes mellitus is strongly associated with the HLA-DR3/4 phenotype. Thus, genetic predisposition may play an important role in the development of this complication.

Financial implications of implementing standards of care for diabetic eye disease.

This article reviews practical financial issues surrounding the implementation of published standards of care for diabetic patients concerning examination for detection of retinopathy. Issues such as the financial basis of referral patterns and the fear of patient loss are raised. The role of the primary physician in coordinating care is discussed. The strategies of ophthalmic screening at the site of primary care are presented as alternatives to published standards. There is a need for development of low-cost screening for low-risk patient groups. All effective means of detecting retinopathy and implementing sight-saving therapy in a timely manner is cost-effective compared with the cost saved of disability payment alone.

Diabetic retinopathy: can we modify its course?

With the exception of panretinal laser photocoagulation, no therapy has been shown to modify the course of diabetic retinopathy. Success in developing new therapies for diabetic retinopathy will depend on how well the disease process is understood and on whether interventions can be identified that ameliorate or circumvent critical stages in the development of the disease. A model of the disease process is presented to serve as a frame-work on which pieces of the puzzle can be placed and new areas of potential interventional therapy can be conceptualized.

Psychosocial correlates of mild visual loss.

Studies of the psychosocial aspects of visual impairment have emphasized the effects of blindness, giving relatively little attention to the effects of mild or partial visual impairment. Consequently, we know little about when in the course of visual loss significant psychosocial dysfunction develops. To address this question, we assessed psychosocial functioning at three times over eight months in 31 adults with proliferative diabetic retinopathy and mild to moderate visual impairment in at least one eye. Examination of the correlations between visual and psychosocial measures revealed strong and significant correlations between visual acuity and adjustment (range of r = -0.45 to -0.68), between visual acuity and psychological symptoms (range of r = -0.39 to -0.50), and between visual acuity and emotion-focused coping (range of r = -0.38 to -0.53). The strength of these correlations and their occurrence in three independent measures of psychosocial functioning suggest a clinically meaningful relationship between visual and psychosocial functioning in the range of mild to moderate visual impairment. Psychosocial dysfunction related to visual impairment develops long before blindness. Further prospective research on the psychosocial aspects of partial visual impairment will clarify this relationship and may help justify early intervention with rehabilitation in the visually impaired who do not qualify for services for the blind.

Clinical photon correlation spectroscopy evaluation of human diabetic lenses.

Clinical research on cataract prevention requires an in vivo assessment of the lens of the eye that is non-invasive, quantitative and detects lens changes that precede lens opacification or cataract formation. The method of photon correlation spectroscopy or quasi-elastic light scattering spectroscopy provides such a non-invasive probe. The measurement, based on fluctuations in scattered light intensity caused by translational Brownian motion of the lens proteins, allows a determination of a protein diffusion coefficient and hence information on quaternary conformational changes of these protein scatterers. These protein changes have been observed in association with the presence of lens opacification. The occurrence of these changes prior to opacification, however, has still to be established. The analyses performed in this study were aimed at testing the hypothesis of an association between subclinical molecular changes in the lens as measured by quasi-elastic light scattering and the presence of selected risk factors for cataract. Measurements were made from 393 diabetics attending the Joslin Diabetes Center Eye Unit and 38 non-diabetic volunteers. Measurements at two different instrument sample times, 1.5 microseconds and 150 microseconds, allowed characterization of two different protein size distributions contributing to the quasi-elastically light scattered signal. Measurements performed at the 1.5 microseconds sample time demonstrated significantly decreased lens protein diffusivity in association with older age, higher grade of nuclear sclerosis and presence of diabetes. Statistically significant associations were also observed between lens protein diffusivity and diabetes related factors such as glycosylated hemoglobin level (diabetes control), duration of diabetes, age at onset of diabetes and type of diabetic therapy. The pattern of association exhibited between decreased protein diffusion coefficient and risk factor status is consistent with the patterns of increased risk previously demonstrated in cataract formation. Measurements performed at the 150 microseconds sample time demonstrated significantly decreased lens protein diffusivity in association with increasing age, female sex and glycosylated hemoglobin level. These associations differed significantly from those observed at the 1.5 microsecond sample time, thereby suggesting that these two sample times assess different species of lens proteins. The results of this analysis demonstrate the clinical utility of quasi-elastic light scattering as a rapid, non-invasive method to quantitate lens changes and assess methods of cataract prevention and treatment.

Risk factors for progression of background retinopathy in long-standing IDDM.

Risk factors for the development of severe forms of diabetic retinopathy were examined prospectively in a group of 153 patients with long-standing insulin-dependent diabetes mellitus. During a 4-yr follow-up study, 34 individuals progressed to preproliferative and proliferative retinopathy. The risk of progression to severe forms of diabetic retinopathy was determined by the degree of background diabetic retinopathy and several systemic factors. It increased steeply with hemoglobin A1c, declined proportionally with increasing age, and was dramatically different in patients with diastolic blood pressure below versus above 70 mmHg. Although the mechanisms of action of these systemic factors are unclear, the findings emphasize the multifactorial nature of the pathogenesis of severe forms of eye lesions.

Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus.

Only one third of patients with juvenile-onset insulin-dependent diabetes seem to be susceptible to diabetic nephropathy. To test whether this susceptibility is related to a predisposition to hypertension, we investigated the association of nephropathy with markers of risk for hypertension. We randomly selected 89 patients with insulin-dependent diabetes from a roster of children and adolescents who were seen between 1968 and 1972 at about the time the diagnosis was made. These 89 patients were recalled for examination, as young adults, in 1986 and 1987. Patients with nephropathy (cases, n = 33) were compared with controls without nephropathy (n = 56). Having a parent with hypertension tripled the risk of nephropathy (odds ratio, 3.7; 95 percent confidence interval, 1.4 to 10.1). Moreover, cases had significantly higher values for maximal velocity of lithium-sodium countertransport in red cells than controls (mean maximal velocity +/- SE, 0.51 +/- 0.04 vs. 0.38 +/- 0.02 mmol per liter of cells per hour; P less than 0.05). The excess risk associated with both these indicators of a predisposition to hypertension was evident principally in patients with poor glycemic control during their first decade of diabetes; the odds ratios were 4.5 (95 percent confidence interval, 1.1 to 18.7) for patients with a parental history of hypertension and 7.7 (95 percent confidence interval, 1.8 to 33.8) for patients with a maximal velocity of lithium-sodium countertransport greater than or equal to 0.35 mmol per liter of cells per hour. We conclude that the risk of renal disease in patients with juvenile-onset insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Predisposition to hypertension appears to increase susceptibility for renal disease principally in patients with poor glycemic control.

Psychosocial aspects of diabetic retinopathy.

Diabetic retinopathy, particularly in the more advanced stages, poses many difficult psychosocial problems and demands major adjustments by the patient. Our review of this literature has identified specific problems relevant to patient care, future research, and public policy. For example, proliferative retinopathy often leads to at least partial visual impairment, psychiatric symptoms, and difficulties with glycemic control. Partial visual impairment appears to cause as much psychosocial disruption as severe blindness. This suggests that most rehabilitation programs that serve the legally blind may come too late in the course of this illness. This review emphasizes the paucity of past research on psychosocial aspects of diabetic retinopathy and raises some questions for future research.

Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus.

The risk of premature coronary artery disease (CAD) and its determinants were investigated in a cohort of 292 patients with juvenile-onset, insulin-dependent diabetes mellitus (IDDM) who were followed for 20 to 40 years. Although patients with juvenile-onset IDDM had an extremely high risk of premature CAD, the earliest deaths due to CAD did not occur until late in the third decade of life. After age 30 years, the mortality rate due to CAD increased rapidly, equally in men and women, and particularly among persons with renal complications. By age 55 years the cumulative mortality rate due to CAD was 35 +/- 5%. This was far higher than the corresponding rate for nondiabetic persons in the Framingham Heart Study, 8% for men and 4% for women. Angina and acute nonfatal myocardial infarction followed a similar pattern, as did asymptomatic CAD detected by stress test, so that their combined prevalence rate was 33% among survivors aged 45 to 59 years. Age at onset of IDDM and the presence of eye complications did not contribute to risk of premature CAD. This pattern suggests that juvenile-onset diabetes and its renal complications are modifiers of the natural history of atherosclerosis in that although they profoundly accelerate progression of early atherosclerotic lesions to very severe CAD, they may not contribute to initiation of atherosclerosis.

Influence of HLA-DR phenotype and myopia on the risk of nonproliferative and proliferative diabetic retinopathy.

The relationship between HLA-DR phenotype, refractive error, and risk of both nonproliferative and proliferative diabetic retinopathy was studied among 227 insulin-dependent diabetics participating in a case-control study of diabetic retinopathy. In the absence of myopia, risk of both proliferative and nonproliferative diabetic retinopathy was increased for HLA-DR phenotypes 4/0, 3/0, and X/X (HLA susceptible) compared to HLA-DR phenotypes 3/4, 3/X, and 4/X (HLA nonsusceptible). Odds ratios equalled 11.8 and 7.4 respectively. In the presence of myopia this increased risk associated with HLA status was abolished. Myopia decreased the risk of proliferative and nonproliferative diabetic retinopathy among HLA-susceptible individuals, odds ratio equalled .09 and .09, but had no protective influence among HLA-nonsusceptible individuals.

Risk of proliferative diabetic retinopathy in juvenile-onset type I diabetes: a 40-yr follow-up study.

The development of proliferative diabetic retinopathy was studied in three cohorts consisting of 292 patients with recent juvenile-onset, type I (insulin-dependent) diabetes who were followed 20-40 yr beginning in 1939, 1949, and 1959. The risk of this severe eye complication was almost nonexistent during the first 10 yr of diabetes, rose abruptly to its maximum level (approximately 30/100 person-years), and remained at that level for the next 25 yr. This pattern did not vary with sex, age at onset of diabetes, or level of glycemic control during the first 5 yr of diabetes. However, the risk of proliferative retinopathy was strongly related to the level of glycemic control during the several years preceding onset of this complication. This was a dose-dependent relationship, with patients in the highest quartile of the distribution of the index of frequency of hyperglycemia having a 10-fold higher risk than individuals in the lowest quartile. A virtually identical pattern was observed in patients who developed diabetes in 1959 as was observed in those who developed diabetes in 1949 or 1939. In contrast, diabetic nephropathy as evidenced by persistent proteinuria showed a lower incidence in the 1959 than in the 1939 cohort. In conclusion, these incidence data do not support the notion that the risk of proliferative retinopathy is mainly a function of duration of diabetes. Instead, the pattern of occurrence of this severe eye complication in type I diabetes suggests that the process leading to the development of proliferative retinopathy consists of two or more stages and that progression through each stage may be governed by different factors.

Limited joint mobility (LJM) of the hand in patients with diabetes mellitus: relation to chronic complications.

Limited joint mobility (LJM) of the hand was studied by visual examination in 361 diabetic outpatients aged 11 to 83 years, and 45 non-diabetic controls, without evidence of arthritis. LJM was evident in 58% of diabetic subjects and 4% of controls (p less than 0.001). LJM was noted in 131 (55%) of the 238 patients with insulin-dependent diabetes mellitus (IDDM) as opposed to 31 of the 41 patients (76%) with non-insulin-dependent diabetes mellitus (NIDDM). LJM occurred in 60 of the 82 diabetic subjects (73%) receiving insulin therapy who developed diabetes after the age of 35 years. LJM was significantly related to duration of diabetes in the patients with IDDM less than 40 years of age but was not associated with duration in the patients with NIDDM. A significant association of LJM and neuropathy was noted in patients less than 40 years of age with less than 20 years of diabetes. A significant association of LJM and retinopathy was also noted in those less than 40 years of age with less than 30 years of diabetes. There was no association of LJM and nephropathy regardless of age or duration of diabetes.

Multiple factors in the prediction of risk of proliferative diabetic retinopathy.

To identify risk factors for the development of proliferative diabetic retinopathy, we compared 111 patients with longstanding insulin-dependent diabetes who had proliferative retinopathy (cases) with 81 patients with diabetes of similar duration (an average of 26 years) who did not have proliferative diabetic retinopathy (controls). The cases had diabetes that was more difficult to manage, as evidenced by their more frequent blood sugar levels above 200 mg per deciliter (11 mmol per liter) on routine clinic visits (odds ratio, 1.6 for each increment of 10 per cent in the relative frequency), and they expended less effort in managing their diabetes, as indicated by their less frequent testing of urine for sugar (odds ratio, 0.3). Among those who did not have myopia, the cases also had an excess of the HLA-DR phenotypes 4/0, 3/0, or X/X (odds ratio, 10.0). Among those with myopia, these phenotypes did not carry an increased risk of proliferative retinopathy. These results support a multifactorial model for the development of proliferative diabetic retinopathy; however, the mechanisms of action of the identified factors remain unknown.

Psychologic stress and glycemic control: a comparison of patients with and without proliferative diabetic retinopathy.

Using a case/control design, patients with (cases) and without (controls) proliferative diabetic retinopathy were compared using three psychosocial measures: life events, psychiatric symptomatology, and ego development. Cases reported significantly more symptoms. They also demonstrated a modest and significant correlation of negative life events with HgbA1c that was not shown in the controls. When the relationship of life events with glycemic control was explored in cases of varying durations of proliferative retinopathy, we found that the association between negative life events and HgbA1c was accounted for by the cases with a recent onset of retinopathy. Patients in this recent group showed a trend towards more negative life events that decreased with longer duration of proliferative retinopathy. This study suggests that the onset of proliferative retinopathy portends a life crisis during which metabolic control is sensitive to additional life stress and that this association is not found among patients whose illness is more stable.