Accurate Use of Neutrophil/Lymphocyte Ratio in Patients with Age-related Macular Degeneration

We read with great interest the recently published article “Assessment of neutrophil/lymphocyte ratio in patients with age-related macular degeneration” by Ilhan et al.1 In this study, researchers compared the neutrophil/lymphocyte ratio (NLR) between dry and wet age-related macular degeneration (AMD) patients and healthy controls. It was reported that patients with wet AMD have higher NLR compared with dry AMD patients and controls and that dry AMD patients have higher NLR compared with controls. There are some points that we would like to address from this study.

First, when a diagnosis of AMD is made for a patient, the treatment is initiated immediately, whether the type of AMD is dry or wet. AREDS 2 formulation and intravitreal anti-VEGFs are the standardized treatment protocols for the dry and wet types of AMD, respectively.2^,3 In this study, the authors didn't mention whether AMD patient groups were treated, whereas treatment protocols may affect NLR. VEGF and other inflammatory mediators increase in the vitreous of patients with AMD in association with a generally altered cytokine system.4 It has been proven that anti-VEGF agents, i.e., ranibizumab or bevacizumab, administered intravitreally at least partly reach systemic circulation and have anti-inflammatory effects.5–7 Based on this information, in AMD patients who received treatment, NLR may be affected. So, it should be detailed whether the patients received treatment or not in the Materials and Methods section of the paper. Also, in the Discussion section, when the limitations of the study are discussed, elevated levels of VEGF in the vitreous of AMD patients should be mentioned, along with how the AMD treatments may affect the results of the study.

Second, NLR, which integrates the detrimental effects of neutrophilia (an indicator of inflammation) and lymphopenia (an indicator of physiologic stress), has emerged as a useful prognostic marker in many studies, evaluating patients with systemic inflammation.8^,9 In the original study, a leukocyte count >12,000 cells/μL or <4,000 cells/μL was mentioned as one of the exclusion criteria. However, the authors did not state why these values were used as the limits for inclusion. As is known, the leukocyte count reference ranges may vary depending on many factors, such as the population studied, the individual laboratory, and the instruments (e.g. types of collection tubes) or measurement methods used (e.g. waiting period prior to analysis). Moreover, these are not the ranges commonly used for the device used in the original study. Determining inappropriate leukocyte count range may lead to a bias in patient selection.

Third, it would be more appropriate to perform receiver–operating characteristic (ROC) analysis to determine the most appropriate cutoff values for NLR in all patient groups. By performing ROC analysis, the value of NLR and cutoff points with highest sensitivity and specificity would have been determined for patients with AMD to use in clinical practice.

In conclusion, NLR alone without other inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, tumor necrosis factor-alpha, interleukin-6, etc.) has led to the insufficiency of evidence confirming the presence of inflammation and may not accurately provide information about the prognosis of the patients. Evaluating and comparing other inflammatory markers with NLR in this patient group may provide more significant results.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.