IMPORTANCE Biomarkers that predict future visual acuity (VA) in eyes with baseline diabetic macular edema (DME) would substantively improve risk assessment, management decisions, and selection of eyes for clinical studies targeting DME.OBJECTIVE To determine whether baseline or early change in the novel spectral domain-optical coherence tomography (SD-OCT) parameter disorganization of the retinal inner layers (DRIL) is predictive of VA in eyes with center-involved DME.DESIGN, SETTING, AND PARTICIPANTS At a tertiary care referral center for diabetic eye disease, a retrospective, longitudinal cohort study obtained demographics, VA, and SD-OCT images from baseline, 4-month, and 8-month visits in 96 participants (120 eyes) with diabetes mellitus and baseline center-involved DME (SD-OCT central subfield thickness, Ն320 μm for men and Ն305 μm for women). Exclusion criteria included substantial media opacity, cataract surgery within 6 months, and nondiabetic retinal pathology affecting VA. On SD-OCT, the 1-mm-wide retinal area centered on the fovea was evaluated by masked graders for DRIL extent, cysts, hyperreflective foci, microaneurysms, cone outer segment tip visibility, and external limiting membrane or photoreceptor disruption and reflectivity. MAIN OUTCOMES AND MEASURESVisual acuity and SD-OCT-derived retinal morphology. RESULTSGreater DRIL extent at baseline correlated with worse baseline VA (point estimate, 0.04; 95% CI, 0.02-0.05 per 100 μm; P < .001). An increase in DRIL during 4 months was associated with VA worsening at 8 months (point estimate, 0.03; 95% CI, 0.02-0.05 per 100 μm; P < .001). A multivariate model that included a 4-month change in VA, DRIL, and external limiting membrane disruption was predictive of an 8-month VA change (r = 0.80). Each approximately 300-μm DRIL increase during 4 months predicted a 1-line, 8-month VA decline. When DRIL increased at least 250 μm at 4 months, no eyes had VA improvement of at least 1 line at 8 months. When DRIL decreased at least 250 μm at 4 months, no eyes had VA decline of at least 1 line at 8 months, and 77.7% had VA improvement of at least 1 line.CONCLUSIONS AND RELEVANCE Disorganization of the retinal inner layers in the 1-mm foveal area is associated with VA, and change in DRIL predicts future change in VA. Early change in DRIL prospectively identifies eyes with a high likelihood of subsequent VA improvement or decline. Therefore, DRIL warrants further study as a robust, readily obtained, and noninvasive biomarker of future VA response in eyes with DME.

Despite treatment advances, diabetic eye disease remains a leading cause of visual acuity (VA) loss worldwide. No methods to prospectively determine which patients will gain or lose vision exist, limiting individualized risk assessment and management. We investigated whether noninvasive, readily obtainable spectral domain optical coherence tomography parameters were correlated with VA in eyes with current or resolved center-involved diabetic macular edema (DME). Images were evaluated for disorganization of the retinal inner layers (DRIL), cysts, epiretinal membranes, microaneurysms, subretinal fluid, and outer layer disruption/reflectivity. DRIL affecting ≥50% of the 1-mm central retinal zone was associated with worse VA in all eyes, eyes with current edema, and eyes with resolved edema. Furthermore, early 4-month change in DRIL extent predicted VA change from baseline to 1 year. These data suggest that DRIL is a robust predictor of VA in eyes with present or previous DME and more highly correlated with VA than other widely used measures, such as retinal thickness. If further studies confirm DRIL as a predictive biomarker of future VA, physicians would gain a new tool of substantial clinical and investigative importance that could significantly change the approach to ophthalmic counseling and therapeutic management in patients with diabetes.

Sensitive, high-throughput methods to detect malaria parasites in low-transmission settings are needed. PCR-based pooling strategies may offer a solution. We first used laboratory-prepared samples to compare 2 DNA extraction and 4 PCR detection methods across a range of pool sizes and parasite densities. Pooled Chelex extraction of DNA, followed by nested PCR of cytochrome b, was the optimal strategy, allowing reliable detection of a single low-parasitemic sample (100 parasites/l) in pool sizes up to 50. This PCR-based pooling strategy was then compared with microscopy using 891 dried blood spots from a cohort of 77 Ugandan children followed for 2 years in an urban setting of low endemicity. Among 419 febrile episodes, 35 cases of malaria were detected using the PCR-based pooling strategy and 40 cases using microscopy. All five cases of malaria not detected by PCR were from samples stored for >2 years with parasitemia of <6,000/l, highlighting the issue of possible DNA degradation with long-term storage of samples. Among 472 samples collected from asymptomatic children as part of routine surveillance, 15 (3.2%) were positive by PCR-based pooling compared to 4 (0.8%) by microscopy (P ‫؍‬ 0.01). Thus, this PCR-based pooling strategy for detection of malaria parasites using dried blood spots offers a sensitive and efficient approach for malaria surveillance in low-transmission settings, enabling improved detection of asymptomatic submicroscopic infections and dramatic savings in labor and costs.Due to large-scale implementation of effective control measures, many countries where malaria is endemic are experiencing dramatic declines in disease burden. With this success has come a shift in the end goal from control to elimination (9, 10). However, when the goal is elimination, accurate detection of persons infected with malaria parasites becomes essential (11). Standard surveillance systems depend on diagnosis by microscopy, a method that is technically challenging, labor-intensive, and often inaccurate in operational settings. More recently available rapid diagnostic tests (RDTs) provide convenience and ease of use, but they have limitations in specificity, sensitivity, species identification, and cost (22).PCR-based methods for malaria parasite detection are relatively simple and provide improved sensitivity compared to microscopy and RDTs, especially in settings where infections have low parasitemia or contain mixed species (22). PCR can also be performed on dried blood spots, which are convenient for collection, storage, and transport. Nonetheless, PCR has a long turnaround time, making it an impractical tool for clinical care of individual patients. One exception would be real-time PCR, which has a short turnaround time but carries with it cost and capacity constraints that make it unavailable for rapid diagnosis in most settings. However, there is a potential role for PCR in situations where large numbers of samples are being screened: a high-throughput system could allow accurate, rapid, and cost-effective ass...

Background Many hospitals require all operative specimens be sent to pathologists for routine examination. Although previous studies indicate this practice increases medical cost, it remains unclear whether it alters patient management and whether it is cost-effective. Questions/purposes We therefore (1) determined the rate of discordance between clinical and histologic examinations of routine operative specimens during elective primary arthroplasties, (2) determined the cost of routine histologic screening, and (3) estimated its cost-effectiveness in terms of cost per quality-adjusted life year gained, as compared with gross examination or no examination. Methods We retrospectively reviewed medical records of 1247 patients who underwent 1363 routine elective primary total joint arthroplasties between January 18, 2006 and March 15, 2010. We compared preoperative, postoperative, and histologic diagnoses for each patient and categorized them into three classes: concordant (clinical and histologic diagnoses agreed), discrepant (diagnoses differed but with no resultant change in treatment), and discordant (diagnoses differed with resultant change in treatment). Medicare reimbursements were determined through the pathology department's administrative office. Results In 1363 cases, 1335 (97.9%) clinical and histologic diagnoses were concordant, 28 (2.1%) were discrepant, and none were discordant. Total reimbursement for routine pathological examination was $139,532, or $102.37 per specimen. The average cost to identify each discrepant case was $4983.29. Routine histologic examination did not alter patient management, and there was no direct gain in quality-adjusted life years. Conclusions Our observations show routine histologic examinations of routine operative specimens during elective primary arthroplasties increase medical cost but rarely alter patient management and are not cost-effective. Level of evidence Level I, economic and decision analyses. See Guidelines for Authors for a complete description of levels of evidence.