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.

Characteristics after cataract extraction or secondary lens implantation among patients screened for the Endophthalmitis Vitrectomy Study.

PURPOSE: This report describes the presenting clinical ophthalmic features and historical findings in patients with a clinical diagnosis of endophthalmitis after cataract extraction or secondary lens implant surgery screened for enrollment in the Endophthalmitis Vitrectomy Study (EVS). DESIGN: Clinic-based, cross-sectional study. PARTICIPANTS: Eight hundred fifty-four patients suspected to have endophthalmitis after cataract extraction or secondary lens implantation. METHODS: As part of the screening process for the study, an eye examination, a medical history, and demographic data were recorded in standardized form for all patients with endophthalmitis after cataract extraction or secondary lens implant surgery referred to the clinical centers, regardless of whether the patient met entry criteria. MAIN OUTCOME MEASURES: Demographics, presenting signs, and symptoms. RESULTS: The median age of individuals presenting with suspected bacterial endophthalmitis was 75 years (range, 9-100 years). Most of those screened (57.7%) were women. Seventy-nine percent of patients sought treatment within 6 weeks of surgery. Blurred vision, conjunctival injection, pain, and lid swelling were the predominant presenting symptoms in order of prevalence. Ocular pain and hypopyon, widely regarded as diagnostic of endophthalmitis, were each absent in 25% of patients. The median hypopyon height, when present, was 1.5 mm. CONCLUSIONS: The classic presentation of postoperative endophthalmitis includes reduced vision, conjunctival hyperemia, pain, hypopyon, and lid swelling within days after cataract surgery or secondary lens implantation. These were the prominent clinical findings in the EVS as well. Because pain and hypopyon, although common, were not always present, clinicians must be vigilant in postsurgical monitoring of patients.

Microbiologic yields and complication rates of vitreous needle aspiration versus mechanized vitreous biopsy in the Endophthalmitis Vitrectomy Study.

PURPOSE: To compare the microbiologic yields and complication rates associated with vitreous needle tap and vitreous biopsy in the Endophthalmitis Vitrectomy Study (EVS). METHODS: Of 420 EVS patients with postoperative endophthalmitis, 201 received immediate vitreous tap or biopsy (without pars plana vitrectomy) by random assignment and 193 completed 9-12 months of follow-up. Vitreous specimens were obtained by biopsy with a 20-gauge vitrectomy cutting instrument or by needle tap with a 22-27-gauge needle. If resistance to aspiration by needle tap was noted, a vitreous biopsy was performed. RESULTS: Of 201 patients undergoing tap or biopsy, 70 (35%) had needle tap, 127 (63%) had mechanized biopsy, and 4 (2%) had initial needle tap that was aborted to mechanized biopsy ("abort" eyes). Intraoperative hyphema occurred in 2 tap eyes (3%), 3 biopsy eyes (2%), and 0 (0%) abort eyes. Postoperative retinal detachment developed in 8 (11%) tap eyes, 10 (8%) biopsy eyes, and 0 (0%) abort eyes (not significant). Respective rates of culture and gram stain positivity were 69% and 42% in tap eyes and 66% and 41% in biopsy eyes (not significant). The rate of severe visual loss (final acuity <5/200) was significantly higher in tap eyes (16 eyes, 24%) compared with biopsy eyes (13 eyes, 11%) and abort eyes (0 eyes, 0%; P = 0.043). The difference was largely explained by the greater proportion of virulent organisms in the tap eyes compared with biopsy eyes. When visual acuity outcome was defined by other thresholds (20/40 and 20/100), the difference was not significant. CONCLUSIONS: This study showed no significant differences between mechanized vitreous biopsy and needle tap with respect to microbiologic yield, operative complications, short-term (9-12 months) retinal detachment risk, or visual outcome. Choice of vitreous sampling procedure must depend on the clinical judgment of the surgeon.

Additional procedures after the initial vitrectomy or tap-biopsy in the Endophthalmitis Vitrectomy Study.

OBJECTIVE: The study aimed to assess the frequency, indications, and outcome of additional ocular procedures after initial treatment of vitrectomy (VIT) or tap-biopsy (TAP) for patients with endophthalmitis after cataract extraction. DESIGN: The study design was an analysis of observational data collected as part of a multicenter, randomized clinical trial. PARTICIPANTS: Of the 420 patients enrolled in the Endophthalmitis Vitrectomy Study, the 148 who had additional procedures were compared with the 272 who did not. MAIN OUTCOME MEASURES: The types, indications, and number of additional ocular procedures were assessed. A masked examiner measured visual acuity 9 to 12 months after study entry. RESULTS: Within 1 week of study entry, 8% of VIT eyes and 13% of TAP eyes underwent additional procedures, 14% for complications of the initial procedure and 86% for worsening ocular inflammation or infection. Cultures were obtained in 33 of the 38 eyes operated on for worsening inflammation or infection and were positive in 42%. Cultures obtained from the early additional procedures were positive more frequently in eyes with an initial TAP (71%) than in eyes with an initial VIT (13%). Both virulence of initial microbiologic organism isolated and poor presenting vision were risk factors for requirement of reoperation. In all cases in which a single organism was cultured at the initial procedure, when the reculture was positive, it was the same organism. Late additional procedures (after 7 days) were required in 27% of patients. Visual outcome was much worse for eyes that had an additional procedure compared to eyes that did not, and this was especially the case for eyes that had an early additional procedure. Only 15% of eyes that had an early additional procedure achieved 20/40 visual acuity as compared to 57% of eyes that did not. CONCLUSION: Need for an additional procedure was a marker of more severe disease, and patients who underwent additional procedures achieved poorer visual acuity at final follow-up.

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.

An investigation of the hospital charges related to the treatment of endophthalmitis in the Endophthalmitis Vitrectomy Study.

PURPOSE: The purpose of the study is to assess the hospital charges associated with the treatment of endophthalmitis using a sample of patients from the Endophthalmitis Vitrectomy Study (EVS). METHODS: The Endophthalmitis Vitrectomy Study was a multicenter, randomized clinical trial with a two-by-two factorial design to compare immediate pars plana vitrectomy to tap-biopsy and to compare the use of systemic antibiotics (intravenous) to no intravenous antibiotics in the management of postoperative endophthalmitis. Hospital charge data were collected retrospectively from 129 patients from the 4 clinical centers participating in this ancillary study. This represents 31% of the total Endophthalmitis Vitrectomy Study population. An analysis of variance was used to compare hospital charges across center and treatment. A charge-effectiveness analysis compared measures the effectiveness across treatment groups. The annual savings of hospital charges in the United States was estimated for a range of annual incidence rates of endophthalmitis. RESULTS: The use of intravenous antibiotics significantly increased hospital charges. Patients undergoing vitrectomy had significantly higher hospital charges than did patients undergoing tap-biopsy. The most charge-effective treatment for patients presenting with light perception only vision was immediate vitrectomy, whereas the most charge-effective treatment for patients presenting with better vision was tap-biopsy. Factors other than treatment independently associated with hospital charges were female sex, history of diabetes, symptom of red eye, and baseline vision of light perception only. CONCLUSIONS: Assuming the results of the Endophthalmitis Vitrectomy Study were used as a guide for the treatment of endophthalmitis, the estimated annual nationwide reduction of hospital charges would be between $7.6 million and $40.0 million.

The Endophthalmitis Vitrectomy Study. Relationship between clinical presentation and microbiologic spectrum.

PURPOSE: The authors determine if specific features of the clinical presentation of acute postoperative endophthalmitis correlated with the microbiologic culture results. METHODS: A total of 420 patients who had clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation were evaluated as part of a randomized clinical trial. Results of cultures performed on aqueous and vitreous specimens obtained at presentation were categorized as follows: gram-positive coagulase-negative micrococci, "other" gram-positive, gram-negative, and equivocal/no growth. RESULTS: Eleven features of the initial clinical presentation were associated with significant differences in the microbiologic spectrum (P < 0.05). Baseline factors correlating with higher rates of both gram-negative and other gram-positive isolates were: corneal infiltrate, cataract wound abnormalities, afferent pupillary defect, loss of red reflex, initial light perception-only vision, and symptom onset within 2 days of surgery. Gram-negative organisms did not grow in any eyes in which a retinal vessel could be visualized, and 61.9% of these eyes had equivocal or no growth. Diabetes mellitus was associated with a higher yield of gram-positive, coagulase-negative micrococci. Eye pain was not a discriminator for culture results. CONCLUSIONS: The presenting characteristics of acute endophthalmitis after cataract surgery may be helpful in predicting the most likely culture results. Such predictions do not appear sufficiently strong to guide the initial empiric choice of intravitreal antibiotics.

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.

Optimal management of postoperative endophthalmitis and results of the Endophthalmitis Vitrectomy Study.

The Endophthalmitis Vitrectomy Study was a multicenter randomized clinical trial. A total of 420 patients who had developed acute endophthalmitis after cataract surgery were randomly assigned to undergo vitrectomy or tap and biopsy and to receive either systemic antibiotics (ceftazidime and amikacin) or no systemic antibiotics. At 9 months patients were assessed for final visual acuity and media clarity. There was no difference in final visual acuity or media clarity whether or not systemic antibiotics were used. Patients who presented with hand motion acuity or better did not show a benefit from immediate vitrectomy. However, patients who presented with light-perception-only visual acuity had substantial benefit over immediate vitrectomy, with a threefold (33% vs 11%) increased frequency of achieving 20/40 vision or better, double the frequency of achieving 20/100, and a decrease by half in the frequency of severe visual loss to less than 5/200. These differences were statistically significant.

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.

Treatment of endophthalmitis after cataract extraction.

BACKGROUND: A series of 34 patients was prospectively treated for postoperative endophthalmitis according to a specific protocol. The data are from the pilot study performed before initiation of the Endophthalmitis Vitrectomy Study (EVS). METHODS: Patients with bacterial endophthalmitis that developed within 6 weeks of cataract extraction received intravitreal amikacin and vancomycin, subconjunctival and topical antimicrobials and corticosteroids, and systemic corticosteroids. All patients had diagnostic samples removed from the aqueous and vitreous, with randomized assignment to immediate vitrectomy versus vitreous tap and treatment with or without intravenous antibiotics. Outcome was evaluated 3 and 9 months after treatment. RESULTS: At the 9-month visit, visual acuity was 20/50 or better in 49% of all eyes, 20/200 or better in 79%, and 5/200 or better in 91%. Media clarity was such that a "20/40 or better view" of the retina was present in 71% of patients at 3 months and in 97% at 9 months. CONCLUSION: This is one of the largest series of patients with postoperative endophthalmitis treated and evaluated under a prospective protocol and without selection bias. Each of the options used in this study to treat postoperative endophthalmitis may result in good visual results.

Augmentation laser for proliferative diabetic retinopathy that fails to respond to initial panretinal photocoagulation.

PURPOSE: A study was performed to determine if diabetic subjects who fail to respond to initial panretinal photocoagulation with regression of retinopathy risk factors do better with supplemental panretinal photocoagulation. METHODS: Thirty-five patients with 3 or more retinopathy risk factors who failed to respond to panretinal photocoagulation with regression to less than 3 retinopathy risk factors by 3 weeks after initial panretinal photocoagulation were prospectively randomized to augmentation laser panretinal photocoagulation (MORE) or to no additional treatment (NOMORE). RESULTS: Six months after initial treatment, the MORE group (n = 16) had regressed a mean of -0.94 retinopathy risk factors (with 95% confidence interval [CI] -1.60 to -0.26), compared with -0.21 retinopathy risk factors (95% CI -0.69 to 0.27) in the NOMORE (n = 19) group (P = 0.055). However, by 1 year, there was no statistically significant difference in the amount of regression of retinopathy risk factors with a mean decrease of -1.12 (95% CI -2.0 to -0.24) versus -1.05 retinopathy risk factors (95% CI -1.80 to -0.28) in the 2 groups, respectively. Similarly, for visual acuity, there was no difference in outcome. For all study patients, the persistence of three or more retinopathy risk factors was associated with a poorer visual result than if there was regression to less than three retinopathy risk factors. CONCLUSION: This study shows that although augmentation panretinal photocoagulation achieved faster regression of retinopathy risk factors, by 1 year, there was no difference in either mean regression of retinopathy risk factors or visual acuity between eyes treated or not treated with augmentation panretinal photocoagulation. In addition, the study shows that the persistence of 3 or more retinopathy risk factors 1 year after treatment was associated with a poorer visual result. Because sample size limited the power of the study to find small differences between groups, and because in proliferative diabetic retinopathy small differences could be important clinically, the authors do not recommend changes in current clinical practice.

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.

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.

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.

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.