1. Copyright restrictions may apply JAMA Ophthalmology Journal Club Slides: Plus Disease in Retinopathy of Prematurity Hewing NJ, Kaufman DR, Chan RVP, Chiang MF. Plus disease in retinopathy of prematurity: qualitative analysis of diagnostic process by experts. JAMA Ophthalmol. Published online May 23, 2013. doi:10.1001/jamaophthalmol.2013.135.

2. Copyright restrictions may apply Introduction Plus disease diagnosis: –Determines need for treatment: Cryotherapy for Retinopathy of Prematurity (CRYO-ROP), Early Treatment for Retinopathy of Prematurity (ETROP). –“Venous dilation and arterial tortuosity of posterior vessels.” Standard photograph: minimum amount of abnormality. Newer “pre-plus” category. –Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) and ETROP: ≥2 quadrants? Same 2 quadrants? –Which are the key vessels? Few severe vessels enough? –Both adequate tortuosity and dilation needed? –Does peripheral retina matter? Other features?

3. Copyright restrictions may apply Introduction International Classification for Retinopathy of Prematurity (ICROP; 1980s) specified standard parameters: –Zone, stage, clock-hour extent, plus disease. Previously: –Qualitative examination of retinal features. What is plus disease? –Is “arterial tortuosity and venous dilation” an oversimplification? –Could this explain variability in diagnoses? Study Objective: –To examine the diagnostic reasoning process of experts for plus disease in retinopathy of prematurity (ROP) using qualitative research techniques.

4. Copyright restrictions may apply Study Design: –Capture and encode detailed qualitative thoughts of experts during plus disease diagnosis. –Videotaped while reviewing 7 wide-angle images: (1) think-aloud protocol, (2) specific questions. Participants: –6 experts. –CRYO or ETROP principal investigators (5/6), ≥5 ROP articles (5/6), practiced before publication of CRYO-ROP findings (5/6). Data Analysis: –Transcription, review, content analysis using qualitative research methods. Methods

5. Copyright restrictions may apply Results: Think-Aloud Protocol Interexpert Agreement in Plus Disease Diagnosis by 6 ROP Experts From Reviewing 7 Wide-Angle Images a Imperfect agreement: rich data set for understanding rationale of diagnosis.

6. Copyright restrictions may apply Results: Think-Aloud Protocol Interexpert Agreement Among Experts Ranking Severity of Overall Vascular Abnormality, Arterial Tortuosity Alone, and Venous Dilation Alone in ROP a Are experts looking at different vascular features, or considering their importance differently?

7. Copyright restrictions may apply Results: Think-Aloud Protocol Intraexpert Agreement in Plus Disease Diagnosis by 6 ROP Experts From Reviewing 7 Wide-Angle Retinal Images a Intraexpert differences in plus disease diagnosis, significant inconsistencies while looking at the same image twice.

8. Copyright restrictions may apply Results Example: Qualitative Rationale Expert 1: “…looks like a very low gestational age baby; it’s taken quite a long time to get to this stage. There is a lot of arterial tortuosity [annotated]; there is a little bit of venous congestion in the superior temporal and superior nasal quadrant, more in the superior half of the retina [annotated]. By definition I think this has to be plus, because it’s 2 quadrants at least, and even the other quadrants aren’t normal...” Expert 2: “…there is a lot of tortuosity of the arteries; the veins are about 2 to 1. This could either be a pre-plus eye or a normal variant, depending on a quick look to the periphery. Curiously, there is a lot of tortuosity down here [annotated]; it looks like there is disease up here [annotated].” Expert 4: “…vessels seem to be branching excessively in that region [superonasal area annotated] and some increased tortuosity [superotemporal area annotated] as well, and this vein looks too fat [superotemporal area annotated]. If all the quadrants were like this quadrant [superotemporal] then it would be at least pre-plus and verging on plus, but since it’s only 1 quadrant that’s highly questionable, would not classify it as plus. I could see why some would call it pre-plus … I would call it no plus.”

9. Copyright restrictions may apply Results: Specific Questions Relationship Between Perceived Vascular Abnormality and Overall Plus Disease Diagnosis a Expert diagnosis is not always consistent (circled) with plus disease definitions. More studies and clarification to help?

10. Copyright restrictions may apply Results: Features Mentioned by Experts Retinal Features Considered by Experts During Plus Disease Diagnosis a

11. Copyright restrictions may apply Comment There are inconsistencies in plus disease diagnosis. Current concept of plus disease (“arterial tortuosity and venous dilation”) may be oversimplified. – Experts do not always appear to be considering the same retinal features. – Some experts seem to be considering features beyond arterial tortuosity and venous dilation in the posterior pole. Findings may be applied to design of algorithms for computer-based diagnosis of plus disease.

12. Copyright restrictions may apply If you have questions, please contact the corresponding author: –Michael F. Chiang, MD, Departments of Ophthalmology and Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239 (chiangm@ohsu.edu). Funding/Support This work was supported by grant EY19474 from the National Institutes of Health (Chiang), the Dr Werner Jackstaedt Foundation (Hewing), the Friends of Doernbecher Foundation (Chiang), unrestricted departmental funding from Research to Prevent Blindness (Chan and Chiang), and the St Giles Foundation (Chan). Conflict of Interest Disclosures Dr Chiang is an unpaid member of the scientific advisory board for Clarity Medical Systems. Contact Information