Article

Evaluation of a combined index of optic nerve structure and function for glaucoma diagnosis.

Glaucoma Service, Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
BMC Ophthalmology (Impact Factor: 1.44). 02/2011; 11:6. DOI: 10.1186/1471-2415-11-6
Source: PubMed

ABSTRACT The definitive diagnosis of glaucoma is currently based on congruent damage to both optic nerve structure and function. Given widespread quantitative assessment of both structure (imaging) and function (automated perimetry) in glaucoma, it should be possible to combine these quantitative data to diagnose disease. We have therefore defined and tested a new approach to glaucoma diagnosis by combining imaging and visual field data, using the anatomical organization of retinal ganglion cells.
Data from 1499 eyes of glaucoma suspects and 895 eyes with glaucoma were identified at a single glaucoma center. Each underwent Heidelberg Retinal Tomograph (HRT) imaging and standard automated perimetry. A new measure combining these two tests, the structure function index (SFI), was defined in 3 steps: 1) calculate the probability that each visual field point is abnormal, 2) calculate the probability of abnormality for each of the six HRT optic disc sectors, and 3) combine those probabilities with the probability that a field point and disc sector are linked by ganglion cell anatomy. The SFI was compared to the HRT and visual field using receiver operating characteristic (ROC) analysis.
The SFI produced an area under the ROC curve (0.78) that was similar to that for both visual field mean deviation (0.78) and pattern standard deviation (0.80) and larger than that for a normalized measure of HRT rim area (0.66). The cases classified as glaucoma by the various tests were significantly non-overlapping. Based on the distribution of test values in the population with mild disease, the SFI may be better able to stratify this group while still clearly identifying those with severe disease.
The SFI reflects the traditional clinical diagnosis of glaucoma by combining optic nerve structure and function. In doing so, it identifies a different subset of patients than either visual field testing or optic nerve head imaging alone. Analysis of prospective data will allow us to determine whether the combined index of structure and function can provide an improved standard for glaucoma diagnosis.

0 Bookmarks
 · 
82 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study examines the ability of time domain optical coherence tomography (Stratus OCT) of the retinal nerve fiber layer (RNFL) to discriminate between normal patients and patients with three stages of glaucomatous vision loss in a US veteran population. A review of consecutive patients who underwent automated perimetry and Stratus OCT Fast RNFL scanning within a 6-month period was conducted. Patients with nonglaucomatous ocular disease that might affect the RNFL or perimetry results were excluded. Glaucomatous eyes were staged using the Hodapp-Parrish-Anderson grading system. Average, quadrant, and individual clock hour RNFL thicknesses and normative results between all groups were compared. A total of 247 normal subjects and 157 glaucoma subjects were included. Significant differences in RNFL thickness measurements were observed between all groups (p < 0.05). Receiver operating curve analysis of highest area under the curve showed average RNFL for normal versus mild glaucoma (0.86), inferior quadrant for mild versus moderate glaucoma (0.80), and superior quadrant for moderate versus severe disease (0.86). Normative results for individual parameters demonstrated high specificity but low sensitivity for mild disease versus normal control subjects with increasing sensitivity and decreasing specificity in subsequent stages of disease. The number of OCT parameters classified as borderline or abnormal increased with advancing disease, but a combination of high sensitivity and specificity was not detected for any stage. Optical coherence tomography RNFL thickness measurements, individual parameter normative results, and the number of parameters classified as borderline or abnormal poorly distinguished between severities of disease. Significant RNFL thickness overlap and lack of normative parameters demonstrating both high sensitivity and specificity between consecutive stages of disease highlighted the wide variability of structural findings using time domain OCT in the staging of glaucoma.
    Optometry and vision science: official publication of the American Academy of Optometry 04/2014; · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE. To improve the detection of glaucoma, techniques for assessing local patterns of damage and for combining structure and function were developed. METHODS. Standard automated perimetry (SAP) and frequency-domain optical coherence tomography (fdOCT) data, consisting of macular retinal ganglion cell plus inner plexiform layer (mRGCPL) as well as macular and optic disc retinal nerve fiber layer (mRNFL and dRNFL) thicknesses, were collected from 52 eyes of 52 healthy controls and 156 eyes of 96 glaucoma suspects and patients. In addition to generating simple global metrics, SAP and fdOCT data were searched for contiguous clusters of abnormal points and converted to a continuous metric (pcc). The pcc metric, along with simpler methods, was used to combine the information from the SAP and fdOCT. The performance of different methods was assessed using the area under receiver operator characteristic curves (AROC scores). RESULTS. The pcc metric performed better than simple global measures for both the fdOCT and SAP. The best combined-structure metric (mRGCPL&SAP pcc, AROC = 0.868 ± 0.032) was better (statistically significant) than the best metrics for independent measures of structure and function. When SAP was used as part of the inclusion and exclusion criteria, AROC scores increased for all metrics, including the best combined structure-function metric (AROC = 0.975 ± 0.014). CONCLUSIONS. A combined structure-function metric improved the detection of glaucomatous eyes. Overall, the primary sources of value-added for glaucoma detection stem from the continuous cluster search (the pcc), the mRGCPL data, and the combination of structure and function.
    Investigative ophthalmology & visual science 01/2014; · 3.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR) where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.
    PLoS ONE 01/2014; 9(2):e87113. · 3.73 Impact Factor

Full-text (2 Sources)

View
23 Downloads
Available from
Jun 2, 2014