Among the 44 patients (85 eyes) who received long-term HD due to ESKD enrolled in this study, only 11 patients (17 eyes, 20%) still had DME, and ERM was found in 7 (8.24%) eyes. Eighty-five (100%) eyes had abnormal circulation in the retina, such as capillary nonperfusion, microaneurysm and IRMA, which indicated that the condition of DR in these patients was still serious, although 12 of them had received intravitreal anti-VEGF drug injection, and 2 had received intravitreal dexamethasone implant injection. However, the patients enrolled in this study did not receive any form of anti-VEGF or glucocorticoid treatment within the past 6 months, and the lower incidence of DME in this study may be related to long-term HD. Hwang et al. [16] evaluated the effect of HD on CRT and SFCT in a study including 15 DME patients with DN and reported that the average CRT decreased from 317.92 ± 91.41 µm to 287.77 ± 57.55 µm after the first HD and that the SFCT decreased from 313.31 ± 85.89 µm to 288.81 ± 92.02 µm after the first HD.
The occurrence and progression of DME are related not only to ocular factors such as VEGF overexpression caused by retinal ischemia, retinal capillary hyperpermeability, and retinal pigment epithelial (RPE) damage but also to the hypoproteinaemia caused by DN [17, 18, 19]. Since both DR and DN are chronic vascular diseases, the severity of DR is associated with the severity of DN, and DR can be used as a marker to predict the severity of DN [20, 21]. Intensive glycemic control is not only essential for preventing the occurrence and progression of DR and DME but also important for reducing the risk of DN progression.
For patients with ESKD, HD remains the most common treatment modality for improving quality of life and prolonging survival [6]. During regular HD sessions, even if the patient still has severe DR, HD and glycemic control are almost all treatment strategies. Similar to the 44 patients in this study, these patients no longer received ophthalmic treatment for DME or DR. Although epidemiological research has shown that the incidence of DME in diabetes patients is approximately 5.5% [22], that in DR patients reaches 21.1% [23], and that in patients with proliferative DR (PDR) is as high as 66.2% [24]. Since the severity of DN is positively correlated with the severity of DME and DR [25], theoretically, the incidence of DME is greater in patients with DN and PDR.
In this study, we found that the incidence of DME in patients undergoing HD was only 20%. After HD, the average plasma osmolality decreased by 13.17 ± 16.60 mOsm/kg (P < 0.001), and the average body weight decreased by 2.59 ± 0.80 kg (P < 0.001). Both the volume and composition of extracellular fluid decreased dramatically, causing body weight and plasma osmolality to decrease after HD [26], which may be one of the reasons for the low incidence of DME in ESKD patients undergoing HD.
Among the 44 patients (85 eyes) enrolled in this study, 17 (20%) had DME, and all had CME. Among them, ERM was present in 7 eyes with DME (8.24%). The lack of regression of these CMEs after long-term HD may be related to the presence of advanced glycation end products (AGEs). Methylglyoxal (MGO) derived from AGEs may induce alterations in the characteristics of cystoid lesion components in diabetic CME due to posttranscriptional modification, leading to resistance of fibrin in CME to plasmin [27, 28].
ERM is a pathology caused by fibrocellular proliferation on the ILM followed by intravitreal injections for DME treatment or secondary to a wide variety of diseases, such as DN and cataract surgery [29, 30]. ERM formation causes anteroposterior and tangential forces in the retina, resulting in further damage to the blood retina barrier (BRB), the release of inflammatory factors and the deterioration of DME [31]. Clinical studies have revealed that vitrectomy has a beneficial effect on the management of DME with ERM [32].
Fang et al. [33] conducted a two-year study on 108 patients with DME who received intravitreal injections of anti-VEGF drugs to estimate changes in the glomerular filtration rate (eGFR), confirming that although DME can improve with anti-VEGF intervention, the eFGR continues to deteriorate.
Therefore, ophthalmologists should pay close attention to the renal function of patients while using anti-VEGF drugs or corticosteroid intravitreal injections to treat DME in clinical practice. If renal dysfunction meets the HD treatment standard, patients should be promptly referred to nephrologists. For DME patients who are unresponsive or have a poor response to anti-VEGF or glucocorticoid therapy, it is necessary to evaluate renal function as early as possible. Improving renal function may be more conducive to improving DME in patients with ESKD.
To clarify the impact of HD on the retina and choroid, we used SS-OCTA to analyze the CRT, CRV, SFCT and SFCV in patients before and after HD. We found that there was no significant change in the average CRT or CRV before and after HD, while the average SFCT decreased significantly from 243.11 ± 77.15 µm to 219.20 ± 72.84 µm, with a mean reduction of 23.91 ± 14.15 µm (P < 0.001), and the average SFCV decreased significantly from 0.15 ± 0.10 mm3 to 0.13 ± 0.90 mm3, with a mean reduction of 0.28 ± 0.23 mm3 (P < 0.001), after HD. Before the next HD, the average SFCT recovered to 245.41 ± 76.23 µm, and the SFCV recovered to 0.16 ± 0.10 mm3. There was no statistically significant difference in the CRT (P = 0.206), CRV (P = 0.154), SFCT (P = 0.108) or SFCV (P = 0.174) before the two HDs.
This finding may be related to the fact that the choroid is mainly composed of blood vessels, and HD leads to the elimination of water and small molecule metabolic waste, such as BUN and creatinine, in the patient's body. The blood volume in the systemic circulation, including the choroidal vascular system, decreases in a short period of time [34].
In this study, we also observed that within 30 minutes after HD, the average weight of patients decreased by 2.59 ± 0.80 kg (P < 0.001), and the average IOP decreased by 0.07 ± 0.63 mmHg (P = 0.282). However, the renal function of patients with ESKD tends to fail, and the water and metabolic waste discharged previously can gradually accumulate again after HD. Therefore, the SFCT and SFCV of patients in this study increased again before the next HD.
However, the retinal thickness did not change due to HD, which may be related to the fact that the patients in this study had already undergone long-term HD; subsequently, long-term HD led to the stabilization of the macular anatomical structure of the retina. Moreover, retinal blood vessels run between the nerve fiber layer and the inner nuclear layer, while the layers outside the inner nuclear layer in the retina are avascular [35]. Even if HD leads to a decrease in blood volume throughout the body, including in the retinal vascular plexus, its impact on retinal thickness is difficult to detect.
Although all the patients in this study have undergone long-term HD, their renal function is relatively stable, and DME has significantly improved, it cannot be denied that all patients still had severe DR, including the presence of nonperfused capillaries in the retina, focal avascular zone (FAZ) enlargement, and IRMA in 85 (100%) eyes. RNV was still observed in 42 (49.41%) eyes. Patients with ESKD could not be examined by fundus fluorescence angiography. The basis for distinguishing IRMA and RNV was to observe the location of blood flow signals on cross-sectional OCTA images. The blood flow signal of the IRMA is located below the ILM, and if the blood flow signal protrudes from the ILM and enters the vitreous cavity, it is considered an RNV [36, 37].
These RNVs still pose a risk of causing vitreous hemorrhage and traction retinal detachment [38]. However, the impact of ESKD on quality of life and survival time may make these patients more inclined to receive frequent HD rather than ophthalmic treatment. Therefore, ESKD patients with DR still need to receive timely treatment from ophthalmologists to permanently preserve their limited vision.
The main limitation of this study was its small sample size. Further large-scale prospective studies are needed to further clarify the impact of long-term HD on the retina, choroid and optic nerve.