References
Drusen, AMD, tumor necrosis
AGE-RELATED MACULAR DEGENERATION, TUMOR NECROSIS, RETINA, DRUSEN
The Beckman clinical classification of age-related macular degeneration (AMD) [Red-free fundus snap-shot. (Flow Diagram of the study’s participants. Of the 110 patients who enrolled in the study, 55 were randomized to the study group, and 55 to the control group. Fourteen patients did not complete the trial due to loss of follow-up. Forty-six patients in the study group and fifty in the control group completed the study.Suggested mechanisms of the anti-inflammatory and immunomodulatory effects of HCQ. 1. HCQ has a hydrophilic nature, can pass through cell membranes easily and accumulates in intracellular vesicles, including lysosomes, endosomes and autophagosomes. 2. Raising the pH in the acidic vesicles precludes proper functioning of vesicular enzymes. 3. HCQ prevents the presentation of peptides for major histocompatibility complex (MHC)-II, by interfering with the conversion of antigens to peptides in antigen-presenting cells. Hence, extracellular material may accumulate less under the retina. 4. HCQ prevents peptides from interacting with MHC-II in the loading compartment of acidic endosomes on MHC-II. 5. HCQ inhibits cytokine release by interfering with MHC-II-related autoantigen presentation to cluster of differentiation (CD) 4+ T-cells, via antigen-presenting cells. This prevents CD4+ T-cells from activating B-cells. HCQ causes autoreactive T-cells from undergoing apoptosis and obstructs B-cells from processing antigens. The result is impaired function and production of cytokines, including interleukin [IL]-1, IL-6, interferon-gamma, tumor necrosis factor and B-cell activating factor. 6. The binding of immune complexes to TLR7 and TLR9 results in the downstream stimulation of type-1 interferon transcription. Type-1 interferons trigger the generation of additional cytokines by activating T-cells, B-cells, natural killer cells, myeloid dendritic cells and monocytes. The binding of TLR7 and TLR9 to the immune complexes is directly inhibited by the accumulation of HCQ in endosomes that contain TLR7 and TLR9. HCQ can potentially hinder the processing of TLRs by raising the pH of the endosome. Thus, HCQ reduces the transcription of type-1 interferons by interfering with TLR7 and TLR9 signaling; this has immunomodulatory and anti-inflammatory effects.Demographic characteristics and baseline ocular characteristics of the study (hydroxychloroquine) and control (placebo) groups.OCT: optical coherence tomography; Sd: standard deviation.Drusen volume growth as calculated by area and height, measured using optical coherence tomography.