Diabetes complications and glycemic control. The Pittsburgh Prospective Insulin-Dependent Diabetes Cohort Study Status Report after 5 yr of IDDM.

The relationship between glycemic control and complications of insulin-dependent diabetes mellitus (IDDM) remains controversial. With the use of glycosylated hemoglobin (HbA1) to assess glycemic control from diagnosis onward, the Pittsburgh Prospective Insulin-Dependent Diabetes Mellitus Cohort Study prospectively evaluated 80 new cases of IDDM diagnosed at Children's Hospital of Pittsburgh. This study presents findings in 62 patients at 5 yr postdiagnosis. Only 7 patients, all girls, had any retinopathy (microaneurysms). These subjects had an elevated 5-yr mean HbA1 compared to those with no retinopathy (13.0 vs. 11.7%; P less than .05). Six female subjects who had an elevated albumin excretion rate (AER; greater than or equal to 20 micrograms/min) had a higher 5-yr mean HbA1 (13.3%) than the 26 subjects with AER less than 20 micrograms/min (11.8%; P less than .05). Current HbA1 was correlated with AER (r = +.36, P less than .05) and systolic blood pressure (r = +.49, P less than .01) in females. However, these associations were not observed in males. Positive correlations were found between HbA1 (5-yr mean and current) and serum triglyceride and cholesterol, but only in females was HbA1 inversely related to high-density lipoprotein cholesterol. However, HbA1 was independent of sex, HLA-DR type, and urine C-peptide status. Age adjustment did not change the above results. These analyses suggest that glycemic control is related to AER, systolic blood pressure, presence of microaneurysms, and serum triglyceride and cholesterol concentrations during the first 5 yr of IDDM. However, these associations appear to be predominant in girls.

Contribution of diabetes duration before puberty to development of microvascular complications in IDDM subjects.

The contribution of diabetes duration, both pre- and postpuberty, to the development of microvascular complications and mortality in diabetic subjects was investigated in three study populations from the Children's Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) Registry. Life-table analyses by total and postpubertal IDDM duration were used to evaluate differences in the prevalence of microvascular complications and diabetes-related mortality in subjects diagnosed before and during puberty, as defined by an age at IDDM onset marker of 11 yr for girls and 12 yr for boys. The prevalence of retinopathy and overt nephropathy in 552 White adult diabetic subjects (population 1, mean IDDM duration 20.8 yr was significantly greater in subjects diagnosed during puberty compared with those diagnosed before puberty. However, similar analyses by postpubertal duration showed no difference in microvascular complication prevalence between the two groups. These findings did not appear to be due to a confounding effect of age. Additional analyses of 239 adolescent diabetic subjects (population 2, mean duration 8.3 yr) revealed the same trend for the prevalence of retinopathy. Finally, results concerning the risk of diabetes-related mortality in a cohort of 1582 subjects (population 3, mean duration 12.9 yr) indicated that postpubertal duration of IDDM may be a more accurate determinant of the development of microvascular complications and diabetes-related mortality than total duration, and it is suggested that the contribution of the prepubertal years of diabetes to long-term prognosis may be minimal.

A psychophysical technique for measuring cone photopigment bleaching.

A new, clinically applicable test has been developed to measure the bleaching of the foveal cone photopigments. This noninvasive test is called steady-state color matching. Steady-state color matching is based on the dependence of a color match on the optical density of the cone photopigments. By measuring the color match as a function of retinal illuminance, it is possible to compute the optical density of the cone photopigments at each illuminance. Thus, abnormalities of photopigment bleaching can be detected. This study demonstrates that the technique is readily performed by a clinical population. Patients with central serous retinopathy and retinitis pigmentosa are shown to have low effective optical densities.

Cone photopigment bleaching abnormalities in diabetes.

We have used a color-matching technique to obtain estimates of the optical density of cone photopigments as a function of retinal illuminance in patients with insulin-dependent diabetes mellitus (IDDM). We found that the half-bleach illuminance of some patients is abnormally high. That is, it takes more light to bleach an equivalent amount of photopigment in these patients. Since low illuminance color matches for these patients are normal, this implies that these patients have normal amounts of photopigment, but the photopigment is not bleaching normally. This result clearly points to abnormalities in the outer retina of these diabetic patients. The most likely causes of this abnormality are either decreases in the ability of the cones to absorb light, or an increased rate of regeneration of the cone photopigments.

Intraocular distribution of intravitreally administered amphotericin B in normal and vitrectomized eyes.

A study was performed to determine how amphotericin B is distributed in the eye after direct intravitreal injection. Radiolabeled amphotericin B was administered by direct injection into the vitreous space of unmodified phakic control or vitrectomized aphakic eyes in the rabbit model. The eyes were removed at different post-injection times, frozen and dissected into anatomical subparts of cornea, aqueous, iris, lens, vitreous and sclera-choroid-retina. The parts were assayed for total radioactivity (expressed as remaining amphotericin B). No accumulation of drug was observed in the cornea, lens, iris or aqueous region. The majority of drug was found in the vitreous cavity. The rate of disappearance of radiolabeled drug or radiolabeled drug degradation products from the vitreous space was similar to the rate of disappearance from the eye. However, progressive accumulation of radioactivity was observed in the sclera-choroid-retina tissue in the unmodified phakic eyes. This was not observed in vitrectomized aphakic eyes. The accumulated radioactivity could have represented drug degradation products or active drug. These results shed light on the distribution of amphotericin B in the eye after direct intravitreal injection, a procedure often employed clinically for fungal endophthalmitis.

The endophthalmitis vitrectomy study.

Endophthalmitis after cataract surgery can be a disastrous complication that may result in functional loss of an eye. All patients with this problem should receive direct injection of intravitreal antibiotics. The roles of initial vitrectomy and of intravenous antibiotics in treating this condition are controversial. Through a prospective, randomized, clinical trial, these issues can be assessed. We encourage ophthalmologists close to each clinical center to refer patients with postoperative endophthalmitis to these clinics. Questions concerning the Endophthalmitis Vitrectomy Study can be addressed to the principal investigator at the nearest clinical trial center.

Choroidoretinal vascular anastomosis.

Vascular anastomoses between the retina and choroid may occur in different congenital and acquired conditions. It has been postulated that the direction of blood flow in these anastomoses follows a pressure gradient characterized as follows: choroidal artery greater than retinal artery greater than retinal vein greater than choroidal vein. Of the four possible directions of blood flow between the two circulations that this theory allows, only three have previously been reported. The fourth, described in this report, is a choroidoretinal vascular anastomosis with blood flow from a choroidal vessel into a retinal vein.

Punctate outer retinal toxoplasmosis.

Classic ocular toxoplasmosis initially involves inner retinal layers and is associated with marked vitreous reaction. We encountered three cases of punctate outer retinal toxoplasmosis, a subset of ocular toxoplasmosis that is characterized by multifocal gray-white lesions at the level of deep retina and retinal pigment epithelium and that is associated with little or no overlying vitreous reaction. Acute lesions may resolve to form fine granular white dots. Recognition of this uncommon presentation of toxoplasmosis is important, since there is some evidence that treatment of toxoplasmosis may be effective.

Combined ocular infection with cytomegalovirus and cryptococcosis.

To our knowledge, this is the first published description of the clinical and pathologic features of combined ocular infection with both cytomegalovirus and Cryptococcus. Infection occurred in a patient treated by immunosuppression and corticosteroid therapy. This article emphasizes that ocular findings may be the first sign of disseminated opportunistic infection and that clinical manifestations may be sufficient to allow accurate diagnosis of opportunistic retinitis.

Management of ocular penetration from injection of local anesthesia preceding cataract surgery.

We herein describe 12 patients who suffered penetration or perforation of the globe during injection of a local anesthetic before cataract surgery. Minimum follow-up was 6 months. Six eyes had a final visual acuity of 20/50 or better and an attached retina. Four eyes had an attached retina with a visual acuity of 20/80 to 2/200. Two eyes were anatomic failures because of a recurrent retinal detachment complicated by proliferative vitreoretinopathy. These cases show that retinal penetrations without retinal detachment may be treated effectively with photocoagulation. Vitreous surgery is recommended when the retinal penetration is associated with a retinal detachment. Eyes with a dense vitreous hemorrhage and a suspicion of a penetrating injury should either be followed up closely with echography or should undergo vitreous surgery since the extent of the injury cannot be determined.

Endogenous Aspergillus endophthalmitis in drug abusers.

One of two cases of endogenous Aspergillus endophthalmitis in abusers of intravenously administered drugs was treated successfully by subtotal pars plana vitrectomy; amphotericin B administered by intravitreal, periocular, and systemic routes; and flucytosine administered systemically. Aspergillus sp should be considered a possible pathogenic organism in drug abusers with endogenous endophthalmitis. An aggressive diagnostic and therapeutic approach may result in preservation of useful vision.

Diabetes and postoperative endophthalmitis in the endophthalmitis vitrectomy study.

OBJECTIVES: To determine whether there was a different response to vitrectomy and tap/biopsy with or without systemic antibiotic treatment in the Endophthalmitis Vitrectomy Study and whether the signs and symptoms of endophthalmitis differ between diabetic and nondiabetic patients. DESIGN: A multicenter clinical trial in which patients with acute post-cataract extraction endophthalmitis were randomly assigned in a 2 x 2 factorial design to vitrectomy or tap/biopsy, in each case with or without intravenous antibiotics, and followed up for 9 months. Outcome measures included visual acuity assessed in standardized fashion. RESULTS: Fifty-eight of 420 study patients had diabetes. Diabetic patients had slightly worse vision and ocular media at the baseline assessment. Only 39% of diabetic patients compared with 55% of nondiabetic patients achieved 20/40 final vision. Both diabetic and nondiabetic patients with initial light perception (LP)-only vision had better visual results with immediate vitrectomy. For those with better than LP baseline vision, patients with diabetes achieved visual acuity of 20/40 more often with vitrectomy (57%) than with tap/biopsy (40%), but this difference was not statistically significant. Patients without diabetes did equally well with vitrectomy or tap/biopsy. CONCLUSIONS: For patients with better than LP vision, tap/biopsy is appropriate for those without diabetes. A clinical trial of a sufficient number of diabetic patients with better than LP vision is necessary to determine the best management for this group. At present, initial vitrectomy or tap/biopsy are reasonable approaches for diabetic patients with better than LP vision.

Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study.

OBJECTIVE: To analyze the data for cultures and Gram stains prospectively collected by protocol in the Endophthalmitis Vitrectomy Study. DESIGN: Cultures of aqueous, undiluted vitreous, and (for patients who underwent vitrectomy) vitrectomy cassette fluid obtained from 420 patients were prepared on chocolate agar, in thioglycolate broth, and on Sabouraud dextrose agar; Gram stains of the aqueous and undiluted vitreous were made. Criteria were devised to distinguish true pathogens (confirmed positive cultures) from contaminants. SETTING: Private and university-based retina-vitreous practices and corresponding microbiology laboratories. RESULTS: Compared with the aqueous, undiluted vitreous produced a higher percentage of confirmed positive cultures and higher colony counts on chocolate agar and was more frequently the only source of a positive culture from the eye. Nevertheless, the aqueous and vitrectomy cassette fluid were the only source of a positive culture from the eye in 4.2% and 8.9% of eyes, respectively. The overall yields of chocolate agar and thioglycolate broth were similar. A positive Gram stain from the aqueous or undiluted vitreous was highly predictive of a positive culture from the eye, but a negative Gram stain had little predictive value for the culture result. The overall rate of laboratory-confirmed infection was not statistically significantly higher in the vitrectomy group than in the tap or biopsy group. CONCLUSIONS: The vitreous was a richer source of positive cultures and high colony counts than was the aqueous, either because it is more supportive of bacterial growth or because a somewhat larger inoculum of the vitreous than of aqueous could be obtained. The result of Gram stain should not determine the choice of antibiotic drugs in the treatment of endophthalmitis. Vitrectomy, with culture of the vitrectomy cassette fluid, did not produce significantly more positive cultures than tap or biopsy material, and the procedure should not be performed to improve the microbiological yield.

Immunocytochemical demonstration of prealbumin in the vitreous in heredofamilial amyloidosis.

Vitreous material obtained at pars plana vitrectomy from a patient with heredofamilial amyloidosis with vitreous involvement and control vitreous from a patient without amyloidosis were subjected to immunocytochemical studies. P component (AP), a minor constituent of all amyloid deposits, was found in trace amounts in the familial amyloid vitreous, but other amyloid proteins, which occur in secondary amyloidosis or in primary amyloidosis, were not found. The major amyloid protein in the vitreous in heredofamilial amyloidosis (but not control vitreous) was found to be prealbumin.

Evaluation of vitrectomy machines as a source of false-positive culture contamination in endophthalmitis.

PURPOSE: We sought to determine whether a venturi-aspiration vitrectomy machine could contaminate a vitrectomy culture. METHODS: Ninety vitrectomies were simulated in a hospital operating room and were cultured with standard techniques. An additional 90 control specimens were cultured in the exact same manner, but the vitrectomy machine was not used. Instead, the control specimens were placed directly into a sterile vitrectomy cassette. Contamination rates in the two groups were compared. RESULTS: Contamination occurred in four of 90 vitrectomy-simulation cultures and in three of 90 control cultures. This difference in contamination rate was not statistically significant. CONCLUSIONS: Although the result of a culture of the vitrectomy effluent can be false-positive, the source of contamination is not likely to be the vitrectomy machine.

Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study.

PURPOSE: To determine the microbiologic spectrum and antibiotic susceptibilities of infecting organisms in postoperative endophthalmitis and to evaluate the effects of operative factors on the microbiologic spectrum. METHODS: Patients with bacterial endophthalmitis presenting within six weeks of cataract extraction or secondary intraocular lens implantation (IOL) were evaluated. Cultures and Gram stains were performed on intraocular specimens and susceptibility tests on the isolates. RESULTS: Confirmed microbiologic growth was demonstrated from intraocular specimens from 291 of 420 patients (69.3%). Gram-positive bacteria were isolated from 274 patients (94.2%) with confirmed growth and gram-negative bacteria from 19 (6.5%). Two hundred twenty-six of the 323 isolates obtained (70.0%) were gram-positive, coagulase-negative micrococci, 32 (9.9%) Staphylococcus aureus, 29 (9.0%) Streptococcus species, seven (2.2%) Enterococcus species, ten (3.1%) miscellaneous gram-positive species, and 19 (5.9%) gram-negative species. All gram-positive isolates tested were susceptible to vancomycin. Seventeen gram-negative isolates (89%) were susceptible to both amikacin and ceftazidime and two (11%) were resistant to both. Anterior chamber or secondary IOL implantations were associated with higher rates of infection with gram-positives other than coagulase-negative micrococci than were posterior chamber IOL implantations (P = .022) or primary cataract extractions (P = .024). CONCLUSIONS: Gram-positive, coagulase-negative micrococci predominated in this series. Vancomycin was active against all gram-positive isolates tested. Amikacin and ceftazidime showed equivalent activity against gram-negative isolates. Secondary or anterior chamber lens implantations were associated with a possible spectrum shift toward gram-positive organisms other than the coagulase-negative micrococci.

The inverse electro-oculogram.

An electro-oculogram ratio of less than one was found to be caused by limited ocular excursions under photopic conditions in a patient with a rod-cone dystrophy. Because this inverse electro-oculogram ratio was not caused by a decrease in standing potential under photopic conditions, it should be considered an artefact.

Retinal toxicity of amphotericin B in vitrectomised versus non-vitrectomised eyes.

The retinal toxicity of intravitreally administered amphotericin B was compared in non-vitrectomised versus vitrectomised rabbit eyes. Doses of 5 and 10 micrograms in both groups resulted in transient vitritis but had no effect on electroretinograms. Histopathological examination four weeks after injection showed vitreous cells and minimal areas of retinal necrosis in both groups at 5 or 10 micrograms doses. At these doses vitrectomy did not modify the retinotoxic effects of intravitreally administered amphotericin B. At higher doses marked toxicity was found in both vitrectomised and non-vitrectomised groups.

An epidemiologic approach to the study of retinopathy: the Pittsburgh diabetic morbidity and retinopathy studies.

Diabetic retinopathy was studied in two cohorts of insulin-dependent diabetics (IDDs) from the Children's Hospital of Pittsburgh. The first cohort (n = 696) consisted of IDDs of long duration. Severe retinopathy was self-reported in 70% of this cohort by 30 years duration of diabetes. Associations between severe retinopathy, hypertension and smoking were observed. In order to examine the relationship between metabolic control and early diabetic retinopathy, a second cohort of adolescent IDDs (n = 58) were referred for standardized fluorescein angiography. Sixty-four percent had early retinopathy. None had proliferative changes. Significant differences in individual mean whole blood glycosylated hemoglobin (GHb), averaged over 3 years before angiography, were consistently seen between those with and without early retinopathy. Also, the number of microaneurysms was positively correlated with individual mean GHb. Before the advent of GHb testing, those IDDs who later had retinopathy were more likely to have experienced at least one hospitalization for diabetic ketoacidosis. These observations provide strong support that poor metabolic control preceded the development of diabetic retinopathy. Results are consistent with the hypothesis that improvement of metabolic control early in the course of IDDM may prevent or delay the development of the early changes of diabetic retinopathy.