We greatly appreciate Prof. McLeod's interest and comments on our recent study, titled “Correlation of optical intensity on optical coherence tomography and visual outcome in central retinal artery occlusion” in Retina.1 Prof. McLeod shared with us a three-level grading system of oxygenation-based hypoperfusion maculopathy (OHM) which provided insight to different severities of retinal ischemia.
First, we agree that in OHM Grade 1, superficial inner retina (ganglion cells and their processes) is normoxic, and there is no change in structure and optical intensity in superficial inner retina. In OHM Grade 1, middle retina (inner retinal layer and adjacent plexiform tissues) is hypoxic. On optical coherence tomography, increased reflectivity or optical intensity can be observed in inner nuclear layer and eventually middle layer atrophy in OHM Grade 1. In our previous study, the optical intensity of each retinal layers was quantitatively compared between central retinal artery occlusion and control.2 The results showed that inner nuclear layer had maximum increase of reflectivity. In our study,1 we defined the inner retinal layers including retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer, because in severe cases, the optical intensity in these layers increase, and it was not possible to distinguish their boundaries. Therefore, in OHM Grade 1, although the optical intensity of ganglion cell layers would not change, the optical intensity of inner nuclear layer would increase, and the optical intensity of inner retinal layers would also be increased. So the optical intensity ratio can still be applied to OHM Grade 1.
Second, the OHM grading system provided only ordinal information. As Prof. McLeod mentioned in his letter, there could be some cases which had intermediate grades such as OHM 1/2 or OHM 2/3. This suggests that the current grading system can be further refined to distinguish the different severities of these intermediate stages. Furthermore, the grading of OHM is subjective. The agreement among different graders is still unknown. The optical intensity ratio is a quantitative parameter which can objectively characterize any conditions of various severities. Moreover, we found that optical intensity ratio correlated with visual prognosis in eyes with central retinal artery occlusion which supports our claim that optical intensity ratio is a potential biomarker for retina ischemia.
Third, we fully agree that the OHM grading system can be applied to panretinal hypoperfusion from central retinal vein occlusion. Indeed, retinal ischemia, or hypoperfusion can occur in many diseases, some of which involve the whole retina such as central retinal artery occlusion,1 central retinal vein occlusion, ischemic maculopathy in diabetic retinopathy,3 and some of them only involve part of retina, such as branch retinal artery occlusion4 and branch retinal vein occlusion.5 In diseases that involve only part of the retina, pupil assessment may still be normal. An advantage of optical intensity ratio is that it can be measured in specific regions in the diseases which involve only part of retina. In another study, we have observed that optical intensity ratio increased in ischemic maculopathy in branch retinal vein occlusion and was also associated with visual outcome (unpublished data).
Once again, we thank Prof. McLeod for discussing an important issue on the assessment of retinal ischemia or hypoperfusion maculopathy. There are several different methods, including fundus photography, fluorescein angiography, optical coherence tomography, optical coherence tomography angiography,6 retinal oximetry,7 and OHM. Further research will be needed for comparison of the reliabilities of these various techniques.