Validity of code based algorithms to identify primary open angle glaucoma (POAG) in Veterans Affairs (VA) administrative databases.

PURPOSE: The validity of the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9) code for primary open angle glaucoma (POAG) in the Department of Veterans Affairs (VA) electronic medical record has not been examined. We determined the accuracy of the ICD-9 code for POAG and developed diagnostic algorithms for the detection of POAG. METHODS: We conducted a retrospective study of abstracted data from the Michael E. DeBakey VA Medical Center's medical records of 334 unique patients with at least one visit to the Eye Clinic between 1999 and 2013. Algorithms were developed to validly identify POAG using ICD-9 codes and pharmacy data. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity and percent agreement of the various algorithms were calculated. RESULTS: For the ICD-9 code 365.1x, the PPV was 65.9%, NPV was 95.2%, sensitivity was 100%, specificity was 82.6%, and percent agreement was 87.8%. The algorithm with the highest PPV was 76.3%, using pharmacy data in conjunction with two or more ICD-9 codes for POAG, but this algorithm also had the lowest NPV at 88.2%. CONCLUSIONS: Various algorithms for identifying POAG in the VA administrative databases have variable validity. Depending on the type of research being done, the ICD-9 code 365.1x can be used for epidemiologic or health services database research.

Elevated IOP alters the space-time profiles in the center and surround of both ON and OFF RGCs in mouse.

Glaucoma is a leading cause of blindness worldwide, and is characterized by progressive retinal ganglion cell (RGC) death. An experimental model of glaucoma has been established by elevating the intraocular pressure (IOP) via microbead occlusion of ocular fluid outflow in mice. Studies in this model have found visual dysfunction that varied with adaptational state, occurred before anatomical changes, and affected OFF RGCs more than ON RGCs. These results indicate subtle alterations in the underlying retinal circuitry that could help identify disease before irreversible RGC changes. Therefore, we looked at how RGC function was altered with elevated IOP under both photopic and scotopic conditions. We first found that responses to light offset are diminished with IOP elevation along with a concomitant decrease in receptive field center size for OFF RGCs. In addition, the antagonistic surround strength and size was reduced in ON RGCs. Furthermore, elevation of IOP significantly accelerated the photopic temporal tuning of RGC center responses in both ON and OFF RGCs. We found that some of the IOP-induced functional changes to OFF RGCs relied on ON cross-over pathways, indicating dysfunction in inner retinal circuitry. Overall, these results suggest that IOP alters multiple functions in the retina depending on the adaptational state. They provide a basis for designing multiple functional tests for early detection of glaucoma and for circuit-specific therapeutic targets in treatment of this blinding disease.

senseless repression of rough is required for R8 photoreceptor differentiation in the developing Drosophila eye.

An outstanding model to study how neurons differentiate from among a field of equipotent undifferentiated cells is the process of R8 photoreceptor differentiation during Drosophila eye development. We show that in senseless mutant tissue, R8 differentiation fails and the presumptive R8 cell adopts the R2/R5 fate. We identify senseless repression of rough in R8 as an essential mechanism of R8 cell fate determination and demonstrate that misexpression of senseless in non-R8 photoreceptors results in repression of rough and induction of the R8 fate. Surprisingly, there is no loss of ommatidial clusters in senseless mutant tissue and all outer photoreceptor subtypes can be recruited, suggesting that other photoreceptors can substitute for R8 to initiate recruitment and that R8-specific signaling is not required for outer photoreceptor subtype assignment. A genetic model of R8 differentiation is presented.

Identification of novel cellular genes transcriptionally suppressed by v-src.

Our aim is to identify cellular genes whose transcriptional suppression by the v-src oncogene contributes directly and specifically to the transformed and tumorigenic phenotype. We used a modified PCR-based subtractive hybridization technique to isolate 9 cDNAs whose abundance in NIH3T3 fibroblasts is decreased 3-15-fold following transformation by the activated oncogene, v-src. Sequence analysis reveals that 3 cDNAs are unlike those in GenBank. The remaining 6 cDNAs are indentical or highly similar to rat helix-destabilizing protein gene (hnRNP A1), mouse CTLA-2 alpha cysteine protease, rat cytochrome c oxidase (COX) VIc subunit, mouse Type I collagen, human gravin and a partial human cDNA (clone A7C09) isolated by random automated sequencing. Northern blot analysis indicates that the basal level of transcripts in untransformed NIH3T3 of all the genes except mouse Type I collagen was at least 10-fold lower than that of HMG Co-A Reductase, which is abundantly transcribed. These data suggest that the down-regulation of some or all of these genes contributes to v-src-induced changes in mitogenic control or cell morphology.