ivi

Oct 30, 2024

Abstract To determine the correlation between the severity of chronic kidney disease (CKD) and treatment of diabetic macular edema (DME). The retrospective 2-year cohort study included eyes with DME confirmed using spectral-domain optical coherence tomography in Taipei Veterans General Hospital, Taiwan, between 2010 and 2020. All the eyes were treated with an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) during regular follow-up around 2 years. They were categorized into 3 different groups: an estimated glomerular filtration rate ≥ 60 (mL/min per 1.73 m2) (group A), < 60 (group B), and patients undergoing hemodialysis (group C). The main outcome measures were (1) visual improvement, (2) structural improvement, and (3) the injection frequency of anti-VEGF in the different groups. In this study, 167 eyes from 120 patients were enrolled. Compared with groups B and C, the eyes in group A experienced the only significant visual improvement at month 3, month 6, and month 12 (P = 0.0001, 0.0002, 0.0013, respectively). The presence of subretinal fluid and intraretinal cysts was significantly decreased in groups A and B. In the treatment frequency analysis, the number of injections was the highest in group A and lowest in group C during the study period (P = 0.04). The severity of CKD had an impact on the DME treatment. The less severe CKD was, the greater the visual improvement that could be achieved. In addition, relatively poor renal function required a lower anti-VEGF injection frequency. The active prevention of the progression of CKD may play a key role in DME treatment. Introduction Diabetic macular edema (DME) is one of the most common causes of visual disturbance in diabetic mellitus 1 . In previous studies, the presumed pathogenesis of DME has been linked to the breakdown of the blood-retinal barrier 2 , 3 , which is induced by oxidative stress from a prolonged hyperglycemic status. Vascular endothelial growth factors (VEGF) and inflammatory cytokines are upregulated by tissue hypoxia and overexpressed through maintained hyperglycemia. In recent years, based on this pathogenesis, the mainstream treatment of DME has been an intra-vitreal injection (IVI) of anti-VEGF, steroids, or laser photocoagulation 4 . However, these treatment modalities are sometimes unable to provide effective functional and anatomical improvements. Therefore, the development of DME may stem from complex interplay of multiple factors. Abnormal renal profiles and advanced DR usually exist simultaneously, suggesting that they may share similar pathophysiology in a microvasculcar environment 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 . Besides, the severity of chronic kidney disease (CKD) has also increased the attention on the treatment of DME in recent years 13 , 14 , 15 . In theory, the accumulation of extracellular fluid in retinal parenchyma may be eliminated through hemodialysis to some extent 16 , 17 , 18 , 19 , 20 . However, the impact of CKD on DME treatment remains undetermined because most studies have either involved small case numbers, a cross-sectional study design, or a follow-up period shorter than 6 months 13 , 21 , 22 . Therefore, the present study contributes to existing literature in 3 ways. First, we conducted a 2-year retrospective cohort study involving the analysis of 167 eyes. Second, we correlated renal function and DME treatment, including the frequency of treatment and visual improvement. Third, we evaluated the change in macular edema by using optical coherence tomography (OCT) images. Materials and methods Study design and population This retrospective cohort study strictly adhered to the tenets of the Declaration of Helsinki and obtained ethics approval from the Institutional Review Board of Taipei Veterans General Hospital (No. 2018-11-004CC). All the eyes enrolled in the study had been diagnosed with DME according to the medical records between 2010 and 2020 from a single medical center, TVGH. DME was defined as central macular thickness of ≥ 300 μm (in the central 1 mm diameter area) and the presence of subretinal fluid (SRF) or intraretinal cysts (IRCs) in central 3 mm diameter area on spectral-domain OCT images (OptoVue, Fremont, CA, USA). The inclusion criteria were the following: (1) age ≥ 20 years old; (2) DME with the presence of SRF or IRCs and retinal thickening recorded using OCT images; (3) a DR stage evaluated using fundus photography or fluorescein angiography; (4) diabetes mellitus under regular medical treatment; (5) eligible laboratory data related to serum creatinine (Cr), blood urea nitrogen (BUN), and glycated hemoglobin (HbA1C) at baseline and 3 months after initial treatment; (6) a regular follow-up of visual acuity and structural change through an OCT examination every 1–2 months for the cases under treatment, or every 3–6 months for stable cases, during the follow-up period. The exclusion criteria included the following: (1) eyes with other causes of macular edema such as vitreomacular interface disease or retinal vascular disease; (2) eyes that were not receiving regular follow-up in TVGH or did not receive scheduled anti-VEGF IVI during the study period; (3) eyes that received IVIs of any medication within 6 months before enrollment; (4) eyes that had previously undergone vitrectomy; and (5) pregnancy. Three consecutive monthly injections of anti-VEGF were applied as a loading dose for treatment-naïve patients with DME. Subsequently, they received pro re nata treatment as required based on the change in visual acuity, level of edema in the OCT images, and patients’ decision. The follow-up interval was decided by retinal specialists in TVGH based on clinical presentation and treatment response. Data collection Age, sex, diabetic medication, status of hypertension, DR stage at baseline and month 12, status of panretinal photocoagulation, treatment-naïve status, and IVI medications, including 2 mg/0.05 mL of aflibercept (Eylea; Regeneron Pharmaceuticals, Tarrytown, NY, USA), 0.25 mg/0.05 mL of ranibizumab (Lucentis; Genentech, San Francisco, CA, USA), and 1.25 mg/0.05 mL of bevacizumab (Avastin; Genentech), were recorded. Serum Cr, BUN, albumin (Alb), urine albumin and creatinine ratio (UACR), and hemoglobin at baseline were recorded. HbA1C at baseline and month 3 were also recorded. CKD was defined according to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines. All the eyes were categorized into 3 groups according to the baseline estimated glomerular filtration rate (eGFR): eGFR ≥ 60 mL/min per 1.73 m2 (group A), < 60 mL/min per 1.73 m2 (group B), and patients undergoing hemodialysis (group C) 23 , 24 . Best-corrected visual acuity (BCVA) and OCT images were measured and collected at baseline and at months 3, 6, and 12. BCVA was measured using Snellen eye charts and was converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Data on the central macular thickness (CMT) and presence of SRF or IRCs were obtained using spectral-domain OCT, RTVue XR Avanti (Optovue, Inc., Fremont, CA). Statistical analysis The categorical variables between the different groups were analyzed using a Chi-square test or Fisher’s exact test, with adjustments made for multiple testing using the Bonferroni correction. For continuous variables, analysis of variance was performed for age. A nonparametric Kruskal–Wallis test was used to examine the difference in HbA1C, renal parameters, BCVA, OCT characteristics, and the number of injections at different CKD stages. We evaluated the correlation between the frequency of IVI treatment and renal parameters by using Spearman correlation coefficients. A Wilcoxon signed-rank test was used to compare the BCVA and CMT before and 3, 6, and 12 months after treatment. A McNemar test was performed to compare the SRF and IRCs before and 3, 6, and 12 months after treatment. The SRF and IRC status before and 3, 6, and 12 months after treatment at different stages of CKD and DR were evaluated using a Chi-square test. A P-value < 0.05 was considered statistically significant in all the analyses. We used MedCalc statistical software version 19.6.1 (MedCalc Software, Ostend, Belgium; https://www.medcalc.org ; 2020) for all statistical analyses. The Medical Ethics Committee of Taipei Veterans General Hospital has waived the need of informed consent in this study. Results Baseline characteristics This study enrolled 164 eyes from 120 patients. The mean follow-up time was 21.4 ± 4.4 months. Each eye, even within the same individuals, was treated as an independent subject, with distinct consideration for its unique retinal condition and response to treatment. Of these, 147 eyes (87.4%) were treatment naïve. The baseline characteristics were stratified according to different stages of CKD. Of the 164 eyes, 75 with eGFR ≥ 60 (mL/min/1.73 m2) were stratified as group A (average eGFR = 82.2 mL/min per 1.73 m2), 78 with eGFR < 60 were stratified as group B (average eGFR = 39.4 mL/min per 1.73 m2), and 11 from patients undergoing dialysis were stratified as group C(average eGFR = 16.3 mL/min per 1.73 m2)(Table 1 ). Of the 120 patients, 63 were male and 57 were female. Of the 164 eyes, 143 eyes were pseudophakic, 21 eyes were phakic without progression of cataracts during the follow-up period. Age, hypertension, serum hemoglobin, serum BUN, HbA1c, and UACR exhibited statistically significant differences (p < 0.05) in different groups, which were compatible with different renal and systemic condition. Table 1 Baseline characteristics of the eyes in different groups.