Presence of plus disease in retinopathy of prematurity (ROP) is an important criterion for identifying treatment-requiring ROP. Plus disease is defined by a standard published photograph selected over 20 years ago by expert consensus. However, diagnosis of plus disease has been shown to be subjective and qualitative. Computer-based image analysis, using quantitative methods, has potential to improve the objectivity of plus disease diagnosis. The objective was to review the published literature involving computer-based image analysis for ROP diagnosis. The PubMed and Cochrane library databases were searched for the keywords “retinopathy of prematurity” AND “image analysis” AND/OR “plus disease.” Reference lists of retrieved articles were searched to identify additional relevant studies. All relevant English-language studies were reviewed. There are four main computer-based systems, ROPtool (AU ROC curve, plus tortuosity 0.95, plus dilation 0.87), RISA (AU ROC curve, arteriolar TI 0.71, venular diameter 0.82), Vessel Map (AU ROC curve, arteriolar dilation 0.75, venular dilation 0.96), and CAIAR (AU ROC curve, arteriole tortuosity 0.92, venular dilation 0.91), attempting to objectively analyze vessel tortuosity and dilation in plus disease in ROP. Some of them show promise for identification of plus disease using quantitative methods. This has potential to improve the diagnosis of plus disease, and may contribute to the management of ROP using both traditional binocular indirect ophthalmoscopy and image-based telemedicine approaches.