Introduction
Central retinal artery occlusion (CRAO) is a common ophthalmic emergency that often leads to severe vision loss and permanent visual impairment. More apparent retinal damage occurs with longer durations of ischemia [
1]. It was reported the annual incidence of CRAO was about 1.9 in 100,000 people [
2]. CRAO is usually embolic in origin [
1]. The Factors associated with CRAO include cigarette smoking, body mass index, hypertension, diabetes, high serum lipid levels, coagulopathy, and cardiac disease, including atrial fibrillation [
3]. Typically, CRAO manifests as a sudden, painless, monocular loss of visual acuity and peripheral vision [
4]. The presenting visual acuity could vary widely, and the patient may or may not have readily visible fundus abnormalities [
3]. Before progression to a more complete CRAO, paracentral acute middle maculopathy (PAMM) may be the first sign to be noted. With the advent of optical coherence tomography angiography (OCT-A), it is possible to perform depth-resolved imaging and detailed visualization of the retinal capillary system in vivo. OCT-A is helpful in detecting PAMM. PAMM is not an isolated phenomenon but a common sign of several ocular diseases or even systemic conditions [
5‐
7]. PAMM may be caused by ischemia of the intermediate and deep capillary systems, which are responsible for blood supply to the middle retina [
8,
9]. It was reported that approximately 22.38% (32/143) of the Chinese patients with CRAO showed PAMM on spectral domain optical coherence tomography (SD-OCT) [
10]. The association between PAMM and visual acuity in patients with CRAO is still unclear. In this study, we used OCT-A to analyze CRAO in patients with and without PAMM.
Discussion
Characterized by partial or complete occlusion of the central retinal artery, CRAO often leads to catastrophic vision loss. It is the ocular equivalent of an ischemic cerebral stroke [
14]. PAMM refers to retinal lesions with changes in the inner nuclear layer on SD-OCT [
15]. With the advent of OCT-A, PAMM has been considered as vascular pathology resulting from ischemia of deep retinal layers [
16]. Various studies have shown that PAMM is related to retinal ischemia [
15,
17,
18] and is an accompanying symptom of potential retinal vascular disease, representing activated microglial tissue caused by hypoxia and upregulated inflammatory molecules in an attempt to repair ischemic tissue [
19]. B-scan OCT-A has revealed hyperreflective foci dominated by the core layer, with PAMM-like changes disappearing with the thinning of the inner nuclear layer [
8,
16,
20]. In this study, patients with CRAO were divided into the PAMM and no-PAMM groups using OCT-A combined with FFA according to the presence or absence of PAMM-like changes. Both groups analyzed visual acuity and related factors in the affected eyes.
Previously study reported PAMM generally had normal fluorescence on FFA [
21,
22]. We also found it was difficult to detect PAMM by FFA. In the PAMM group, OCT-A could reveal a lack of blood flow signals in the small terminal retinal arteries in the superficial and deep layers and in successive capillary networks. Browning et al. [
23] reported that the appearance of PAMM-like changes might signify mild retinal ischemia. Similarly, we observed many scattered retinal soft exudates in the fundus and PAMM-like hyperreflectivity in the PAMM group. These all indicated retinal ischemia. Therefore, we hypothesized that PAMM-like CRAO might occur due to occlusion a. Unlike the devastating visual impairment of conventional CRAO, it seems to be a self-regulatory mechanism of the body. The small terminal arteries and their connected capillaries regulate vascular resistance by constriction and occlusion, maintaining a constant blood flow in tissues when tissue perfusion pressure changes. OCT-A showed small terminal arteries and capillaries lacking blood flow signal in the PAMM groups, which may be a sign of this mechanism.
In the non-PAMM group, a large area of trunk vessels was observed by FFA and OCT-A, with a broken branch-like absence of blood flow signal and no perfusion area. The increase in macular thickness due to retinal edema was also more significant than that in the other group. Similarly, Abdellah [
19] also reported the macular thickness increased in 66.67% of CRAO cases which indicated macular swelling on ischemia. It may be caused by decompensation loss due to poor perfusion. As observed in the non-PAMM group, all cells in the inner layer of the retina underwent acute swelling in severe retinal ischemia, resulting in hyperreflectivity of the entire inner layer of the retina by B-scan OCT-A, which was a relatively severe manifestation of ischemic damage. A recent study from Feucht reported the inner retinal layers hyperreflectivity in all CRAO cases [
24]. But it did not indicate whether these CRAO case had the accompanying symptom of PAMM.
Similar to the previous report, we found the retinal thickness of the central macular sulcus positively correlated with the LogMAR BCVA in the current study [
25]. We also found the retinal of the central macular sulcus in the no-PAMM group was much thicker. More severe macular edema indicated a higher degree of retinal ischemia, thus leading to worse visual acuity. Ahn S et al. also reported that the initial macular edema in patients with CRAO was significantly related to final BCVA, though the initial BCVA was not record in their study [
26]. These results suggested that the degree of visual function impairment mainly depended on the severity of CRAO. Macular retinal thickness may be a manifestation of the degree of ischemia. Furthermore, the final central macular thickness was related to a poor visual prognosis in retinal artery occlusion [
26,
27]. However, no significant differences in the superficial and deep vascular density were observed between the two groups, which may be caused by the machine’s inability to recognize slow flow. PAMM-like changes might be an essential indicator for distinguishing the degree of impairment. PAMM might be due to hypoxia, and the blood vessels were not completely blocked, leading to hypoxia. However, in CRAO patients without PAMM, full-thickness retinal edema and complete lack of oxygen (anoxia) to the cells might result in poorer visual acuity [
28].
The present study has several limitations. Firstly, it is a single-center and retrospective study. Although consecutive patients were screened for eligibility, selection bias can’t be excluded. Secondly, the sample size was small, and the results need to be confirmed furtherly by a more extensive and prospective study. Lastly, due to the small sample size, CRAO was not further typed based on OCT-A.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (
http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.