Abstract
Purpose: To examine the relationship between rate of vascular change and plus disease diagnosis. Design: Retrospective observational case-control study. Methods: Wide-angle images were taken bilaterally from 37 infants at 31 to 33 weeks and 35 to 37 weeks postmenstrual age (PMA). The semi-automated Retinal Image multiScale Analysis system was used to measure parameters for all arteries and veins: integrated curvature, diameter, and tortuosity index. A reference standard diagnosis (plus vs not plus) was defined for each eye by consensus of 5 experts at 35 to 37 weeks PMA. Weekly rate of change in parameters was compared in eyes with plus vs not plus disease. Receiver operating characteristic area under the curve (AUC) was calculated for plus disease detection based on 1) weekly rates of parameter change between 31 to 33 weeks and 35 to 37 weeks PMA and 2) parameter values at 35 to 37 weeks only. Results: Weekly rates of change in all venous parameters were significantly different in eyes with plus vs not plus disease, particularly for tortuosity index (P < .0004) and diameter (P = .018). Using weekly rate of change, AUC for plus disease detection was highest for venous tortuosity index (0.819) and venous diameter (0.712). Using the 35 to 37-week PMA image only, AUC was highest for venous integrated curvature (0.952) and diameter (0.789). Conclusion: Rate of change in venous, but not arterial, parameters is correlated with plus disease development in this data set. This did not appear to contribute information beyond analysis of an image at 35 to 37 weeks PMA only.
Original language | English (US) |
---|---|
Pages (from-to) | 468-475.e1-e2 |
Journal | American journal of ophthalmology |
Volume | 150 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2010 |
Externally published | Yes |
ASJC Scopus subject areas
- Ophthalmology
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In: American journal of ophthalmology, Vol. 150, No. 4, 10.2010, p. 468-475.e1-e2.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Plus disease in retinopathy of prematurity
T2 - Quantitative analysis of vascular change
AU - Thyparampil, Preeti J.
AU - Park, Yangseon
AU - Martinez-Perez, M. E.
AU - Lee, Thomas C.
AU - Weissgold, David J.
AU - Berrocal, Audina M.
AU - Chan, R. V.Paul
AU - Flynn, John T.
AU - Chiang, Michael F.
N1 - Funding Information: This study was designed to assess the accuracy of computer-based diagnosis of plus disease using quantitative vascular parameters computed at a single session (35 to 37 weeks PMA), compared to the rate of vascular change between 2 sessions (31 to 33 weeks and 35 to 37 weeks PMA). The key findings were that 1) computer-based image analysis has potential to diagnose plus disease based on individual vascular features, and 2) analyzing rate of change in vascular parameters between these 2 sessions has potential to identify plus disease, although this did not appear to contribute information beyond analysis of a single session. Our findings are consistent with earlier work suggesting that computer-based image analysis can identify plus disease based on quantitative vascular features. 9–12,14,16,23–26 In this study, all vascular parameters except for arterial diameter were significantly different in images with plus disease by expert consensus compared to images without plus disease. Using the 35- to 37-week PMA image only, diagnostic accuracy was highest for venous integrated curvature (AUC = 0.952) and diameter (AUC = 0.789). One earlier study using the same computer-based system as the current study found that, for both arteries and veins, all 3 system parameters were significantly larger in eyes with plus disease than in those with no plus disease. 24 In that earlier study, integrated curvature had highest accuracy for diagnosis (AUC = 0.911 for arteries, 0.824 for veins). Another study using this same computer-based image analysis system found that arterial tortuosity index (but not arterial or venous diameter) was significantly higher in images with ROP than in images without ROP. 16 Finally, a study involving a different computer-based system found that images with plus disease had greater average tortuosity and dilation than images without plus disease, but that this difference was statistically significant only for tortuosity. 25 The current study also shows that weekly rate of change in venous parameters was significantly different for eyes that developed plus disease compared to those that did not. AUC for plus disease detection was highest for weekly rate of change of venous tortuosity index (0.819) and diameter (0.712) ( Table 2 and Figure 3 ). This suggests that rate of change in venous parameters is correlated with plus disease development, and that analysis of change in vascular parameters between examination sessions has potential to identify plus disease. However, the AUC for rate of change in vascular parameters was not higher than that for the value of vascular parameters at the second examination session (35 to 37 weeks PMA) alone, indicating that this did not appear to contribute information beyond analysis of a single image at 35 to 37 weeks PMA. Previous research has suggested the potential utility of analyzing the rate of vascular change for identifying severe ROP. Data from the CRYO-ROP study regarding the natural course of disease showed that faster rate of progression to prethreshold disease was associated with worse structural outcomes. 15 Wallace and associates found faster rate of disease progression in infants who had early vascular changes designated “pre-plus disease,” which indicated a greater likelihood of development of severe ROP. 13 Heneghan and associates found absolute change in vascular diameter, but not tortuosity, to be correlated with clinical diagnosis of plus disease. 12 The latter study differed from our current study in that it examined average change in vascular parameters for all vessels, rather than only those vessels present in both images, and in that it did not differentiate between arteries and veins. In this study, we show that change in a greater number of vascular parameters over time is significantly correlated with diagnosis of plus disease. Having said that, we emphasize that plus disease is currently defined by comparison to a standard photograph at a single point in time, and this study did not provide evidence that rate of change in vessel parameters is better at identifying plus disease. Faster rate of anatomic change has been found useful for guiding treatment in other ophthalmologic diseases and in other fields of medicine. Several glaucoma staging systems allow for measurement of quantitative change in optic disc parameters, 27 and faster rate of change in cup-to-disc ratio has been correlated with higher average intraocular pressure. 28 In cardiology, 1 study showed that side-by-side interpretation of echocardiograms, which allow for quantified analysis of parameter change, had higher specificity than interpretation of independent echocardiograms for identifying change in valve regurgitation. 29 Another study in cardiology, which examined electrocardiogram QRS segment duration, found that increase in QRS duration over time was a better predictor of adverse cardiac outcome than a single measurement of QRS duration. 30 For ROP, future studies involving the predictive value for rate of vascular change to identify risk of poor outcomes, compared to traditional methods based on findings at individual exams, may be warranted. A key limitation of this study is that the reference standard was considered to be presence of plus disease at single points in time (either 31 to 33 weeks or 35 to 37 weeks PMA). This was done because the current definition of plus disease is based on individual ophthalmoscopic examinations, without regard to temporal progression. Previous studies involving computer-based plus disease diagnosis have used similar reference standards for comparison. 10,11,13,25,26,31 Because our reference standard was obtained during a static examination, this study design may significantly bias toward showing that computer-based analysis at single points in time perform better than analysis of rates of vascular change for plus disease diagnosis. Larger studies, in which experts and automated image analysis systems are asked to review serial images and provide overall diagnostic impressions regarding disease progression and prognosis, would produce additional insights. We suspect that important information would be gained by considering the temporal progression of vascular change in ROP, and previous work has suggested that video documentation of retinal vascular evolution may contribute diagnostic and educational value. 31 If baseline rates of vascular development can be characterized in normal premature infants, then future ROP classification systems might incorporate these data so that abnormal rates of change could be detected using computer-based methods. Additional study limitations should be noted. First, there was variation in quality among study images. This may have affected quantitative measurements of dilation and tortuosity, particularly if vessel margins were indistinct because of blurring. Among all study images, 13.6% of arteries were of insufficient quality to be analyzed by the computer-based system, whereas only 4.3% of veins could not be analyzed. It is possible that this may have introduced a systematic bias that led to rate of change in arterial parameters being less associated with plus disease than rate of change in venous parameters ( Table 2 ). However, because rates of vascular change were always calculated within the same patients, other possible confounding factors such as image magnification would be expected to remain consistent. Second, because the first imaging session was between 31 and 33 weeks PMA and the second was between 35 and 37 weeks PMA, the number of weeks between examination sessions was not consistent. Although this was addressed by calculating the rates of change per week, understanding the precise time course of vascular evolution in ROP may require further research. Thrid, only 8.8% of study images had a reference standard diagnosis of “plus disease” based on expert consensus. Therefore, future studies examining a larger number of eyes with plus disease will have greater power for examining the rate of vascular change on clinical plus disease diagnosis. In summary, computer-based image analysis has potential to identify plus disease based on individual vascular features. Analysis of temporal change in vascular parameters has potential to provide information regarding plus disease diagnosis beyond what is available during a single examination. Because retinal vessels in ROP evolve significantly within a short time, future research may be warranted to examine the role for creating new indices for disease classification based on rate of vascular change. Disease classification incorporating quantifiable measures such as rate of change may help to decrease subjectivity in plus disease diagnosis. Publication of this article was supported by funding from Research to Prevent Blindness (New York, New York, USA) and grant EY13972 from the National Institutes of Health (Bethesda, Maryland, USA) (M.F.C.). Michael F. Chiang is an unpaid member of the Scientific Advisory Board of Clarity Medical Systems (Pleasanton, California, USA). Involved in design and conduct of the study (P.J.T., Y.P., J.T.F., M.F.C.); collection, management, analysis, and interpretation of data (P.J.T., Y.P., M.E.M., T.C.L., D.J.W., A.M.B., R.V.P.C., J.T.F., M.F.C.); and preparation, review, or approval of the manuscript (P.J.T., Y.P., M.E.M., T.C.L., D.J.W., A.M.B., R.V.P.C., J.T.F., M.F.C.). This study was approved by the Institutional Review Board at Columbia University Medical Center. Written informed consent was obtained from all expert study participants prior to participation, and waiver of consent was obtained for use of de-identified retinal images. This study was conducted in accordance with Health Insurance Portability and Accountability Act (HIPAA) guidelines. Preeti Thyparampil is a graduate of the Columbia University College of Physicians and Surgeons, Class of 2010. Preeti grew up in Queens, New York, and earned a BA in Biology and Psychology from New York University in 2005. She will be a resident in ophthalmology at The Cullen Eye Institute, Baylor College of Medicine in Houston, Texas. Michael F. Chiang is an Associate Professor of Ophthalmology and Biomedical Informatics at Columbia University, New York, New York. His research involves telemedicine, image analysis, and electronic health record systems. Dr. Chiang received a BS in Electrical Engineering and Biology from Stanford University, an MD from Harvard Medical School and Harvard-MIT Division of Health Sciences and Technology, and an MA in Biomedical Informatics from Columbia University. He completed residency and pediatric ophthalmology fellowship training at the Johns Hopkins Wilmer Eye Institute.
PY - 2010/10
Y1 - 2010/10
N2 - Purpose: To examine the relationship between rate of vascular change and plus disease diagnosis. Design: Retrospective observational case-control study. Methods: Wide-angle images were taken bilaterally from 37 infants at 31 to 33 weeks and 35 to 37 weeks postmenstrual age (PMA). The semi-automated Retinal Image multiScale Analysis system was used to measure parameters for all arteries and veins: integrated curvature, diameter, and tortuosity index. A reference standard diagnosis (plus vs not plus) was defined for each eye by consensus of 5 experts at 35 to 37 weeks PMA. Weekly rate of change in parameters was compared in eyes with plus vs not plus disease. Receiver operating characteristic area under the curve (AUC) was calculated for plus disease detection based on 1) weekly rates of parameter change between 31 to 33 weeks and 35 to 37 weeks PMA and 2) parameter values at 35 to 37 weeks only. Results: Weekly rates of change in all venous parameters were significantly different in eyes with plus vs not plus disease, particularly for tortuosity index (P < .0004) and diameter (P = .018). Using weekly rate of change, AUC for plus disease detection was highest for venous tortuosity index (0.819) and venous diameter (0.712). Using the 35 to 37-week PMA image only, AUC was highest for venous integrated curvature (0.952) and diameter (0.789). Conclusion: Rate of change in venous, but not arterial, parameters is correlated with plus disease development in this data set. This did not appear to contribute information beyond analysis of an image at 35 to 37 weeks PMA only.
AB - Purpose: To examine the relationship between rate of vascular change and plus disease diagnosis. Design: Retrospective observational case-control study. Methods: Wide-angle images were taken bilaterally from 37 infants at 31 to 33 weeks and 35 to 37 weeks postmenstrual age (PMA). The semi-automated Retinal Image multiScale Analysis system was used to measure parameters for all arteries and veins: integrated curvature, diameter, and tortuosity index. A reference standard diagnosis (plus vs not plus) was defined for each eye by consensus of 5 experts at 35 to 37 weeks PMA. Weekly rate of change in parameters was compared in eyes with plus vs not plus disease. Receiver operating characteristic area under the curve (AUC) was calculated for plus disease detection based on 1) weekly rates of parameter change between 31 to 33 weeks and 35 to 37 weeks PMA and 2) parameter values at 35 to 37 weeks only. Results: Weekly rates of change in all venous parameters were significantly different in eyes with plus vs not plus disease, particularly for tortuosity index (P < .0004) and diameter (P = .018). Using weekly rate of change, AUC for plus disease detection was highest for venous tortuosity index (0.819) and venous diameter (0.712). Using the 35 to 37-week PMA image only, AUC was highest for venous integrated curvature (0.952) and diameter (0.789). Conclusion: Rate of change in venous, but not arterial, parameters is correlated with plus disease development in this data set. This did not appear to contribute information beyond analysis of an image at 35 to 37 weeks PMA only.
UR - http://www.scopus.com/inward/record.url?scp=77957281442&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957281442&partnerID=8YFLogxK
U2 - 10.1016/j.ajo.2010.04.027
DO - 10.1016/j.ajo.2010.04.027
M3 - Article
C2 - 20643397
AN - SCOPUS:77957281442
SN - 0002-9394
VL - 150
SP - 468-475.e1-e2
JO - American journal of ophthalmology
JF - American journal of ophthalmology
IS - 4
ER -