Our results showed that the prevalence of PPH in eyes with PM was 4.05%. The definition of PPHs was somewhat broader in our study than that for DHs because PPHs included the conus and periconus types of PPHs that had not been reported and were thus specific to PM eyes. Our results showed that the prevalence of the conus-related PPHs (2.81%) was approximately twice as high as the disc-related PPHs (1.47%) in PM eyes. The prevalence of disc-related PPHs (1.47%) in the PM eyes was slightly higher than that of normal subjects (0%-1.08%) but on the very low end of the range of previously reported prevalence of DHs in glaucoma patients (1.45%-36.9%)
9 In addition, a larger number of female patients with PM had PPHs, which we suggest was due to the larger female base with PM.
26,27
Regression analyses (
Table 3) showed that patchy atrophy reduced the risk of a repeat hemorrhaging while an elongation of the axial length increased the risk. These are new findings that show that in addition to the type and stage of glaucoma,
10 the category of myopic maculopathy and axial length were risk factors for recurrences of PPHs in highly myopic eyes. These findings indicate that even though the choroid is thinner in patchy atrophy than in diffuse atrophy, the choroid forms new holes in Bruch's membrane in eyes with patchy atrophy,
28,29 the mechanical stress caused by axial elongation may be released, and the risk of re-hemorrhaging is correspondingly reduced. This explanation needs to be confirmed in future studies.
The eyes in the “possible ON damage” or “possible glaucoma” groups had an increased risk of a recurrence. This provides an additional clue that can help diagnosing glaucoma in PM eyes (i.e., we need to consider the presence of glaucoma or ON damage if PPH recurs repeatedly in PM eyes). Prospective, longitudinal studies focusing on the PPHs and corresponding VF changes may also provide important clues for the pathogenesis and progression of ON damage in PM eyes.
The conus type of PPHs was the most common type (
Table 4), and 85.7% of them were located on the temporal side of the optic disc. Previous studies reported that the parapapillary gamma zone developed and enlarged temporally from the disc border in highly myopic eyes and was usually largest in the temporal parapapillary region.
30,31 These findings indicated that PPA progresses predominantly temporal to the optic disc and that the tissue of the PPA region is thinner
22,32 and more fragile than the normal tissue of the fundus. This leads to a greater tendency for PPHs to develop on the temporal side of the optic disc, and they tend to be the conus type.
The earlier suggested pathogenesis of DHs in glaucomatous eyes
9 might not be appropriate for PPHs in PM eyes especially for the conus-related PPHs. Our FFA results showed that 38.1% of the eyes with PPHs had straightened retinal arterioles that ran from the optic disc, and some of the venules at A-V crossings had an abnormal degree of bending (
Fig. 3). In the eyes with abnormal bending of retinal venules at A-V crossings, capillary telangiectasia and retinal capillary microaneurysms were frequently seen. Hayashi et al.
33 examined the FFA findings of 232 eyes with PM and showed the presence of capillary telangiectasia and capillary microaneurysms in the area with abnormal bending of the retinal veins at A-V crossing. These observations suggest that the sharp bending of the retinal venules at A-V crossings may slow the flow of blood from the retinal capillaries and the post-capillary venules toward the main trunk of the retinal venules as in myopia-induced retinal vein occlusion. It has been suggested that the vascular walls of such telangiectatic capillaries or microaneurysms tend to rupture, which may be one of the causes of PPHs. The stagnation of venous blood could be most prominent near the A-V crossing sites, which may explain why the PPHs tended to be found along the straightened sections of retinal arterioles (viz., at A-V crossing sites).
Interestingly, the retinal tissue in two eyes appeared to be compressed at the hemorrhagic site (
Figs. 4,
5). No previous studies have reported similar findings. Although the pathogenesis of such compression was not determined, we suggest that the retinal arterioles become straightened as they run from the optic disc to the peripheral retina by the axial elongation. Shimada et al.
34 examined vertical OCT sections between the macula and the ON in PM eyes and showed that retinal arterioles were not simply stretched but also protruded anteriorly (Figure 4 in their article). Such a straightening and anterior protrusion of retinal arterioles probably alters the morphology of the surrounding retinal tissue. The FFA findings (
Fig. 4) showed that a group of capillaries and microaneurysms were compressed along the artery, which led to severe dye leakage from these capillaries. The OCT images also showed a compression of the retinal tissue along the retinal artery (
Fig. 4). This is supported by how thick the retina was along the straightened arteriole and instead how thin the retina was on both sides of the compressed tissue (
Figs. 4D–
4G). Such abnormal compression may damage the walls of the retinal capillaries, which would then cause hemorrhaging in and around the compressed area. Based on our findings on the ridges (
Fig. 3), we suggest that the mechanical damage produced by the ridges, such as a direct mechanical force applied to the upper retina or relative compression within the retina, which can damage the blood vessels, is one of the mechanisms for the formation of a PPH.
There are some limitations in our study. First, all our data were collected from patients examined in the Advanced Clinical Center for Myopia at TMDU, which might have led to a selection bias and might not be generalized. Second, the median follow-up interval was 3.03 months, so the PPH we examined may not be on the actual day of the onset of bleeding, and the absorption period we obtained (median, 182 days) may be longer than the actual absorption period. In addition, the PPH might have been missed during the interval. Third, this was a retrospective cohort study, and the impact of the absence of some clinical data and the value of testing not on the PPH day need to be considered. For example, disc-centered OCT examinations were not performed in most patients, leading to a lack of strong evidence for further exploration of the pathogenesis of disc-related PPHs. In addition, the lack of pre- and post-hemorrhagic VF testing makes it difficult to investigate the relationship between PPH and VF. Fourth, because most of the OCT results were obtained from 12 radial scans centered on the fovea, they rarely passed through the center of the PPH site, or if they did, the exact level of PPH might not be obtained due to the small area of the bleeding. Therefore future studies should be prospective with periodic serial FFA examinations or dense raster OCT scans centered on the disc to characterize and quantify the longitudinal changes. These tests should focus on the relationship between retinal vascular changes, PPHs, and VF defects. Fifth, eyes with glaucoma were not excluded from our study because of the difficulty in diagnosing glaucoma in PM eyes. So, a confounding effect of glaucoma is possible.
In conclusion, PPHs are not rare in eyes with PM with a prevalence of 4.05%. The PPHs were most often located in the temporal PPA region of the optic disc. Conus and periconus types of PPHs appear to be specific to PM with a prevalence of approximately twice that of disc-related PPHs. In addition, myopic axial elongation, mild myopic maculopathy, and the presence of glaucoma or ON damage were risk factors for the recurrence of a PPH. The pathogenesis of PPHs in PM eyes is probably different from that in glaucomatous eyes, and it may be mainly related to the mechanical tension generated by PM-associated lesions. These lesions can directly or indirectly damage the vessel walls. Such mechanical forces may play a role in pathologic myopic VF defects.