RMD is thought to be closely related to AMD. The mechanism of RMD is still under investigation. In this study, comparing between 43 RMD eyes EZ thickness and 40 healthy eyes EZ thickness. Our results demonstrate that the EZ thickness of RMD patients is thinner than in healthy subjects. Many studies suggest that RMD is closely related to choroidal lesions(11, 12). Cheng H et al. found that patients younger than 82 years with AMD and RPD had a significantly smaller mean choroidal thickness than in AMD alone (MD-53.72 μm, P = 0.01) (12). Chatziralli I et al. found that the degree of chorionic capillary morphological damage in patients with RMD was higher than that of patients with the same drusen size, and choroidal capillary changes may occur in patients with RMD(11). Because choroidal circulation is the source of blood and oxygen supply to the outer retina, it is essential for maintaining various functions of extra-retinal cells. Therefore, according to the existing research, it can be inferred that RMD may be closely related to choroidal blood circulation, which is consistent with various pathophysiological mechanisms caused by the decrease of posterior blood flow and choroidal structure(13).
Besides choroid-related lesions, studies have shown that RPD is closely related to the damage of the Bruch membrane, and there is a close relationship between pseudoxanthoma elasticum and adult-onset foveomacular vitelliform dystrophy(AFVD) and Sorsby fundus dystrophy. RPD may be caused directly or indirectly damage by Bruch membrane damage(9, 14, 15). Some researchers have found that patients with RPD have significantly reduced macular visual sensitivity compared with patients with typical drusen(16, 17), Alten F et al. used multifocal electroretinography (mf-ERG) and SD-OCT to study the structure of RPD eyes, and functional correlation found that RPD eye visual function decreased over time(18). This means that the cause of RPD is not monofactorial, and the occurrence of RMD is not only accompanied by changes in the choroid but also by the changes in the EZ. The EZ is full of cones and rods, and the high reflection of this band is mitochondria. These two kinds of cells have the characteristic that the disc of them will continue to fall off and synthesize, which tightly related to the mitochondria(19). Therefore, our study measures EZ thickness of the main visual function layer of the retina to explore whether RPD eyes have changes in EZ thickness. The choroidal affecting theory is approbated widely. Our research opens up a new way to explore RMD pathogenesis.
The ellipsoidal zone is what is known as the IS/OS layer. This band contains the inner section of the photoreceptor and is the main visual function layer on the retina(20). The degree of damage to the EZ in most research is based on its integrity and the intensity of the reflection on the OCT. It has been reported that AMD eyes with RPD have ellipsoidal lesions, which is related to cone density reduction(21). Spaide et al. found that eye progression was associated with geographic atrophy and the damage of photoreceptor cell length and destruction of the EZ or the intensity decrease of the EZ(22). However, the measurement of the thickness of the EZ has not been reported.
In the present study, RMD patients have a thinner EZ thickness compared with the normal group (P<0.01). The EZ is the main area where the photoreceptors are located. The photoreceptors are mainly composed of cones and rods. RMD patients' EZ becoming thinner means that the photoreceptors have changed in structure. We postulate this is due to the reduction or atrophy of the cones in this layer. The choroid of RMD patients has obvious capillary lesions, which can directly affect the blood supply of the outer retina(11). Corvi F believes that the occurrence of RPD is related to the shrinkage or fibrosis of choroidal vessels(23). Perhaps it is because the lesion of the choroidal vascular layer leads to insufficient blood supply to the visual function layer, resulting in a decrease or shrinkage of the number of visual function cells.
Furthermore, the current study found that EZ in the central fovea of the RMD patients was significantly thinner than in the control group (P< 0.01). In the central fovea of the macula, has central cone cell bundle which is the most accurate and sensitive part of the macular vision. The damage of cone cells may lead to vision loss, visual distortion, color vision abnormalities. The EZ becomes thinner in the central fovea of the RMD patient, which indicates that the cone cell density is decreased in this region. Wu Z et al. measured the relative intensity of the EZ to study the changes in the inner segment of early AMD(24). The results showed that the EZ reflection intensity of the AMD was significantly lower than in the control group. The thinner EZ and the decreasing intensity of the EZ reflection are all the manifestations of the structure and quantity reduction of visual functional cells. RMD is an essential factor in progression from early to late stage AMD(6). Our experiment results confirm that both RMD and early AMD have ellipsoidal changes, and they may have similar pathogenesis. It also confirms that RMD affects the visual function layer or that RMD is not only accompanied by choroidal changes, but also structural changes in the visual function layer.
In this study, we measured and compared the EZ thickness in the superior, inferior, nasal, and temporal quadrants between the RMD group and the control group and found that the RMD group’s EZ is significantly thinner in all quadrants with the superior quadrant in particular having the thinnest zone. RMD mostly occurs between the superior and upper temporal artery6. Thus, according to our result, the most affected location of the EZ thickness coincides with the predilection site of RMD, which may because that the choroidal blood vessels in superior are more susceptible to damage. However, compared with the change of superior with RMD, the change in the central fovea was greater. Since the central fovea contains only cones and the cone density decreases from the center to peripheral retina, it can be deduced that RMD may decrease the number of cones and lead to atrophy of cones, and RMD patients change on visual function cells mainly acts on cones. However, the specific mechanism still needs further study.
In addition, the study finds that the EZ of RMD males was significantly thinner than in the healthy males (P<0.01); female RMD patients' EZ was thinner than the healthy males with a trend towards significance (P=0.07). According to this result, we may conclude that RMD affects men more than women. The PRD pathology was analyzed by Rudolf M et al. found that RPD lesions contained a large quantity of unesterified cholesterol(25). HDL can reduce free cholesterol in the blood and reduce the deposition of cholesterol in the tissue. Therefore, the effect of RMD on men is greater than that of women.
In the RMD group of this study, nine eyes were accompanied by drusen. Comparing pure RMD eyes with the drusen RMD eyes, the EZ thickness of the pure RMD eyes was not significantly different from the drusen RMD eyes (P = 0.34). Curcio CA pointed out that the occurrence of drusen and RPD is closely related to the material exchange pathway between cones, rods, RPE, Müller cells, and choroidal capillary endothelium, so drusen may have correlation with the change of EZ thickness(5). Our results show that RMD eyes with or without drusen have no difference in EZ thickness.
There are several limitations to our study. First, the EZ thickness was measured manually, which can lead to some deviations so that we cannot obtain the accurate value about the EZ thickness. Second, the sample size is small and without the follow-up to determine whether the thickness will change in a different stage of RMD and when the EZ thickness changed. Though we compared the EZ thickness between the RMD patients with and without RPD, the sample size between these two groups is a great disparity. Third, several types of research have reported that RMD may accompany some systemic disease, but we did not consider whether this systemic factor can influence our results.
In conclusion, The EZ presents hyperreflections on SD-OCT is lead by photoreceptors' mitochondria of photoreceptor cells, which are the key parts of the retinal structure converting light energy into electrical impulses, and is relative to visual function. This finding demonstrates a novel method of studying the pathogenesis of RMD. Our findings reveal that the mechanism of RMD occurs may be related to damage to the mitochondria of photoreceptor cells, which may be one of the mechanisms that RMD occurs.When the impairment degree of mitochondria reach to a certain level, may lead to further vision loss in RMD patients. Therefore, to protect the retinal ellipsoidal zone and its mitochdrial early is important to prevent further impairment of visual function and vision loss. However, the molecular mechanism is not to be confirmed. Further laboratory research will be required. Also, the sample size needs to be expanded, and the measurement method will be optimized to make further exploration and research.