John M. Pach

The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population‐based cohort: The Rochester Diabetic Neuropathy Study

The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency. All Rochester, Minnesota, residents with diabetes mellitus on January 1, 1986, were invited to participate in a cross-sectional and longitudinal study of diabetic neuropathies (and also of other microvascular and macrovascular complications). Of 64,573 inhabitants on January 1, 1986 in Rochester, 870 (1.3%) had clinically recognized diabetes mellitus (National Diabetes Data Group criteria), of whom 380 were enrolled in the Rochester Diabetic Neuropathy Study. Of these, 102 (26.8%) had insulin-dependent diabetes mellitus (IDDM), and 278 (73.2%) had non-insulin-dependent diabetes mellitus (NIDDM). Approximately 10% of diabetic patients had neurologic deficits attributable to nondiabetic causes. Sixty-six percent of IDDM patients had some form of neuropathy; the frequencies of individual types were as follows: polyneuropathy, 54%; carpal tunnel syndrome, asymptomatic, 22%, and symptomatic, 11%; visceral autonomic neuropathy, 7%; and other varieties, 3%. Among NIDDM patients, 59% had various neuropathies; the individual percentages were 45%, 29%, 6%, 5%, and 3%. Symptomatic degrees of polyneuropathy occurred in only 15% of IDDM and 13% of NIDDM patients. The more severe stage of polyneuropathy, to the point that patients were unable to walk on their heels and also had distal sensory and autonomic deficits (stage 2b) occurred even less frequently–6% of IDDM and 1% of NIDDM patients. Overall, two thirds of diabetic patients have objective evidence for some variety of neuropathy, but only about 20% have symptoms, and only 6% of IDDM and only 1% of NIDDM patients have sufficiently severe polyneuropathy to be graded stage 2b, and none were graded stage 3. Approximately one quarter of patients had subclinical carpal tunnel syndrome, but only 7.7% had symptomatic carpal tunnel syndrome. Thus, diabetic peripheral neuropathy is frequent but less severe than generally thought. As generally believed, however, neuropathy, retinopathy, and nephropathy are significantly associated.

Structural and Functional Studies of the Corneal Endothelium in Diabetes Mellitus

We performed specular microscopy, anterior segment ocular fluorophotometry, corneal pachymetry, and tonometry on 14 patients with chronic type I diabetes and nonproliferative retinopathy and on 14 age-matched control subjects. The eyes of patients with diabetes had an increased coefficient of variation of endothelial cell area, a decreased percentage of hexagonal endothelial cells, increased corneal autofluorescence, and increased intraocular pressure, which confirmed previous studies. There was no difference, however, in corneal thickness or endothelial permeability to fluorescein. Thus, we were unable to detect any abnormality in endothelial function in these diabetic corneas in the unstressed state, despite structurally abnormal endothelial cells.

Infectious endophthalmitis after intravitreal injection of antiangiogenic agents.

Purpose: To evaluate the rate of infectious endophthalmitis associated with intravitreal injection of bevacizumab, ranibizumab, and pegaptanib sodium. Methods: A retrospective review of patients who received intravitreal injections of bevacizumab, ranibizumab, and pegaptanib sodium was undertaken. Cases of clinical diagnoses of endophthalmitis or suspected endophthalmitis resulting from intravitreal injection were identified and reviewed. From these data, the risk per injection was estimated. Results: Three patients developed endophthalmitis after the intravitreal injection. The risk per injection was 0.00077 (0.077%). The rate of endophthalmitis was 1 per 1,291 injections. Conclusion: A similar risk of endophthalmitis per injection compared with some trials was obtained in this study. Although no definite risk factors could be identified, intravitreal injections performed by nonretina specialist physicians may be a risk factor for the development of endophthalmitis.

Prognostic Factors in Choroidal and Ciliary Body Melanomas With Extrascleral Extension

In a retrospective study, 50 (8.2%) of 610 patients with malignant melanoma of the ciliary body or choroid had extrascleral extension. Of 46 patients for whom follow-up data were available, 24 (52%) survived five years, 20 (42%) survived ten years, and 17 (37%) survived 15 years. Factors that seemed to affect survival significantly included intraocular tumor size and extraocular tumor size and location. Our observations did not support the role of primary exenteration. Five patients (11%) with extrascleral extension had orbital recurrences and all died within 31 months of surgery regardless of treatment.

Impaired Glycemia and Diabetic Polyneuropathy The OC IG Survey

OBJECTIVE To test whether diabetic polyneuropathies (DPNs), retinopathy, or nephropathy is more prevalent in subjects with impaired glycemia (IG) (abnormality of impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired HbA1c [IA1C]) than in healthy subjects (non-IG). RESEARCH DESIGN AND METHODS Matched IG and non-IG volunteers were randomly identified from population-based diagnostic and laboratory registries, restudied, and reclassified as non-IG (n = 150), IG (n = 174), or new diabetes (n = 218). RESULTS Frequency (%) of DPN in non-IG, IG, and new diabetes was 3 (2.0%), 3 (1.7%), and 17 (7.8%) narrowly defined (no other cause for polyneuropathy) and 19 (12.7%), 22 (12.6%), and 38 (17.4%) broadly defined. Mean and frequency distribution of composite scores of nerve conduction and quantitative sensation tests were not significantly different between IG and non-IG but were worse in new diabetes. Frequency of retinopathy and nephropathy was significantly increased only in new diabetes. In secondary analysis, small but significant increases in retinopathy and nephropathy were found in IGT, IFG, and IGT combined groups. CONCLUSIONS In population studies of Olmsted County, Minnesota, inhabitants, prevalence of typical DPN, retinopathy, and nephropathy was significantly increased only in subjects with new diabetes—not in subjects with IG as defined by American Diabetes Association (ADA) criteria of abnormality of IFG, IGT, or IA1C. For atypical DPN, such an increase was not observed even in subjects with new diabetes. In medical practice, explanations other than IG should be sought for patients with atypical DPN (chronic idiopathic axonal polyneuropathy) who have IG.

Ocular Lymphoma in a Patient With Chronic Lymphocytic Leukemia

PURPOSE To treat large-cell lymphoma in a patient with chronic lymphocytic leukemia and bilateral vitreous cells. METHODS The patient underwent a diganostic vitrectomy. RESULTS Biopsy of the vitreous specimen disclosed large B-cell lymphoma. Large B-cell lymphoma occurring in patients with chronic lymphocytic leukemia is referred to as Richters syndrome. CONCLUSIONS Large-cell lymphoma of Richters syndrome can occur in the eye. This case expands the clinical spectrum of organ involvement in Richters syndrome.

Whipple disease presenting as posterior uveitis without prominent gastrointestinal symptoms

PURPOSE To describe the clinical presentation and course of Whipple disease in an adult. METHODS A 34-year-old man with phthisis bulbi in the right eye secondary to uveitis-induced neovascular glaucoma presented with severe acute posterior uveitis in the left eye. He underwent esophagogastroduodenoscopy and jejunal biopsy for evaluation of anemia. The posterior uveitis was treated with a subtenon injection of triamcinolone. RESULT The diagnosis of Whipple disease was confirmed by polymerase chain reaction analysis of the jejunal biopsy that demonstrated Tropheryma whippelii rDNA. CONCLUSION Although Whipple disease is typically evident with malabsorption, it can also present as uveitis without prominent gastrointestinal symptoms.

Aqueous Humor Dynamics in Patients With Diabetes Mellitus

PURPOSE We measured aqueous dynamic variables in subjects with diabetes mellitus and correlated them with severity of retinopathy and metabolic control to determine whether diabetes affects the anterior circulation of the eye as it affects the posterior (retinal) circulation. METHODS Sixty-one subjects with diabetes mellitus type 1 and 60 subjects with diabetes mellitus type 2 were recruited from the active practice of the Mayo Clinic. Thirty-two normal subjects, divided by age into two overlapping groups of 20 each, served as contemporaneous control subjects. The diabetic subjects were stratified into four groups according to severity of retinopathy. Aqueous humor flow was measured by clearance of topically applied fluorescein with a spectrofluorophotometer; outflow facility was measured by tonography; and intraocular pressure was measured by applanation tonometry. RESULTS In type 1 diabetics, the mean intraocular pressure was slightly greater (14 +/- 3 mm Hg), compared with control subjects (12 +/- 2 mm Hg [P = .002]), while aqueous humor flow was slightly less (2.5 +/- 0.6 microliter/min), compared with control subjects (2.9 +/- 0.5 microliter/min [P = .023]). In type 2 diabetics, the intraocular pressure was 14 +/- 3 mm Hg, which did not differ from that of control subjects (14 +/- 3 mm Hg [P = .258]). Aqueous humor flow in type 2 diabetics (2.5 +/- 0.7 microliter/min) did not differ significantly from that of the control group (2.5 +/- 0.7 microliter/min [P = .961]). Tonographic facility of outflow was not significantly different in type 1 and type 2 diabetics and the control subjects. There was no significant correlation in aqueous humor flow, intraocular pressure, or tonographic facility of outflow to severity of retinopathy or hemoglobin A1c in either type 1 or type 2 diabetics. CONCLUSIONS The dynamics of aqueous humor are not affected to any clinically significant extent in the early or middle stages of diabetic retinopathy. However, there is a tendency toward less aqueous humor flow in the advanced stages of retinopathy.

Neovascularization of the disc in pars planitis.

Neovascularization of the disc (NVD) was present in 9 of 163 patients with pars planitis. In all cases, NVD was unilateral and observed in eyes with recent exacerbation of the inflammatory process. To reduce intraocular inflammation, all nine eyes were treated with varying combinations of topical, periocular, and systemic corticosteroids. In addition to corticosteroids, one eye received Argon laser photocoagulation, two eyes underwent peripheral cryotherapy, and one eye was treated with both Argon laser photocoagulation and peripheral cryotherapy. With decrease or disappearance of intraocular inflammation, NVD resolved in all cases without recurrence during follow-up study, which ranged from 6 to 189 (mean, 81) months. Rhegmatogenous retinal detachments developed in two eyes treated with peripheral cryotherapy. Both detachments were successfully repaired with surgery. Control of intraocular inflammation appears to be the key factor for regression of NVD in pars planitis. If NVD does not regress or vitreous hemorrhage occur, photocoagulation and peripheral cryotherapy may be beneficial.

Increased weakness after pancreas and kidney transplantation.

BACKGROUND Already there is evidence that simultaneous pancreas and kidney (SPK), or pancreas after kidney (PAK) transplantation, in patients with type 1 diabetes mellitus and end-stage kidney disease prevents worsening of diabetic polyneuropathy, but neuropathic improvement is delayed and incomplete. METHODS In 85 patients with type 1 diabetes mellitus who underwent SPK or PAK transplantations, we performed sequential neuromuscular evaluations before, every 3 months after, and yearly after transplantation, quantitating muscle weakness separately from overall severity of polyneuropathy. RESULTS We found that, on average, the weakness subscore of the Neuropathy Impairment Score of the lower limbs [NIS(LL)-W] was significantly worse at 3, 6, 9, and 12 months (by about 5 points) than at baseline. By contrast, for these times after transplantation, a composite score of nerve conduction abnormalities, an independent measure of severity of polyneuropathy, was not significantly worse and, in fact, was significantly improved. In multivariate analysis, length of hospital stay correlated with the increased weakness. CONCLUSIONS We conclude that: (1) increased neuromuscular impairment after transplantation is mainly due to muscle weakness and not to worsening polyneuropathy; (2) in multivariate analysis, duration of hospitalization after transplantation was significantly associated with this increased weakness; (3) increased weakness is probably due to development of myopathy, which may be related to graft rejection, immunosuppression, sepsis, and intercurrent infections; (4) in future transplantation trials, weakness should be evaluated separately from neuropathic status, and the lowest efficacious dosages of immunotherapy should be used; and (5) essentially all diabetic patients reported that SPK or PAK transplantation was worthwhile because it freed them from diabetic lifestyle concerns.