BACKGROUND: Hydroxychloroquine (HCQ) is the first-line treatment for systemic lupus erythematosus (SLE); however, there is heterogeneity in its clinical use. This consensus aims to bridge the gap in SLE treatment by providing practical and valuable recommendations for health professionals.
METHODS: The methodology used is based on a systematic literature review and a nominal group technique (NGT). A ten-member scientific committee formulated eight clinically relevant questions. First, a systematic review was conducted to identify the available evidence, which the scientific committee evaluated to developed recommendations based on their expertise, achieving consensus through NGT.
RESULTS: 1673 titles and abstracts were screened, and 43 studies were included for meeting the inclusion criteria. The scientific committee established 11 recommendations for HCQ use in initiation, maintenance, and monitoring, considering benefits and potential adverse effects of HCQ. Unanimous agreement was achieved on all recommendations.
CONCLUSIONS: The available evidence supports HCQ\'s effectiveness and safety for SLE. Individualized assessment of the initial HCQ dose is important, especially in situations requiring dose reduction or discontinuation. This risk-benefit assessment, specifically focusing on the balance between retinal toxicity and the risk of SLE relapse, should guide decisions regarding medication withdrawal, considering disease activity, risk factors, and HCQ potential benefits. Close monitoring is essential for optimal disease management and minimize potential risks, such as QT prolongation or retinal toxicity.

Background/Objective: Hydroxychloroquine retinopathy, traditionally characterized by parafoveal or pericentral outer retinal damage, is explored for atypical presentations in Asian patients. This challenges conventional beliefs regarding onset, retinopathy pattern, and associated visual field defects. Methods: Ninety-five patients diagnosed with hydroxychloroquine retinopathy at Hanyang University Hospital underwent screening from January 2010 to December 2023. Swept-source optical coherence tomography (SS-OCT), ultra-widefield fundus autofluorescence (UWF-FAF), and automated visual fields (VF) were employed for detailed structural and functional evaluations. Multifocal electroretinography was performed in selected cases requiring additional objective evidence of retinal toxicity. Results: Among 95 patients, 14 (14.7%) exhibited atypical presentations, including very early onset (n = 1), (far) peripheral-dominant damages (n = 4), perivascular involvement (n = 1), bitemporal hemianopsia due to nasal extensive lesions (n = 1), unilateral involvement (n = 2), and asymmetric involvement in retinopathy pattern or severity between the eyes (n = 7). These findings underscore the importance of utilizing expanded imaging techniques, such as ultra-widefield FAF imaging, to identify atypical presentations of retinal involvement. Conclusions: Screening physicians should consider these atypical presentations to ensure timely diagnosis and appropriate management in patients undergoing hydroxychloroquine treatment.

Background and Objective: Hydroxychloroquine sulfate (HCQ) is a lysosomotropic agent administered in systemic lupus erythematosus and rheumatoid arthritis that has fewer toxic effects than chloroquine. However, HCQ may still be responsible for retinal toxicity. In this study, we observed structural changes in the retinas of experimental rats after prolonged exposure to HCQ. Matherials and Methods: We investigated several aspects regarding retinal changes, at both the histopathological and ultrastructural levels. We used 96 male albino Wistar rats distributed into four equal groups (n = 24 per group): the first three groups were treated with different doses of HCQ (50, 100, and 200 mg/kg HCQ, injected intraperitoneally in a single dose daily), and the last group (the control group, n = 24) was treated with saline solution administered in the same way (0.4 mL of saline solution). The treated groups received HCQ daily for 4 months, and every month, six animals from each group were sacrificed to assess retinal changes. The eyes were examined via optical (OM) and electronic microscopy (EM). Statistical analysis was deployed, and results regarding retinal morpho-photometry were acquired. Results: We observed structural retinal changes in both high and low doses of HCQ; while high doses determined a significant thinning of the retina, lower doses caused retinal thickening. Morphological retinal changes upon exposure to HCQ are believed to be caused by accumulated HCQ in lysosomes found in retinal ganglion cells and in the inner nuclear and photoreceptor cell layers. Such changes were most evident in the group receiving HCQ intraperitoneally in doses of 100 mg/kg for a longer period (4 months). Conclusions: The present study highlights histopathological and ultrastructural retinal changes induced by chronic HCQ administration, which were strongly connected to the dosage and period of exposure.

Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading to visual impairment. However, animal models accurately reflecting these pathologies are lacking. Vascular endothelial growth factor A (VEGF-A) is an important factor in the development of micro- and macro-vascular pathology in DR. In this study, we evaluated the feasibility of using a cumate-inducible lentivirus (LV) mediated expression of vegf-a to understand DR pathology in vitro and in vivo. Retinal pigment epithelial cells (ARPE-19) were transduced with cumate-inducible LV expressing vegf-a, with subsequent analysis of vegf-a expression and its impact on cell proliferation, viability, motility, and permeability. Cumate tolerability in adult Wistar rat eyes was assessed as an initial step towards a potential DR animal model development, by administering cumate via intravitreal injections (IVT) and evaluating consequent effects by spectral domain optical coherence tomography (SD-OCT), flash electroretinography (fERG), ophthalmic examination (OE), and immunohistochemistry. Transduction of ARPE-19 cells with cumate-inducible LV resulted in ~ 2.5-fold increase in vegf-a mRNA and ~ threefold increase in VEGF-A protein secretion. Transduced cells displayed enhanced cell proliferation, viability, permeability, and migration in tube-like structures. However, IVT cumate injections led to apparent retinal toxicity, manifesting as retinal layer abnormalities, haemorrhage, vitreous opacities, and significant reductions in a- and b-wave amplitudes, along with increased microglial activation and reactive gliosis. In summary, while cumate-inducible LV-mediated vegf-a expression is valuable for in vitro mechanistic studies in cellular drug discovery, its use is not a feasible approach to model DR in in vivo studies due to cumate-induced retinal toxicity.

(1) Background/Objectives: To investigate the nationwide screening practices and trends in tamoxifen retinal toxicity (tamoxifen retinopathy) in South Korea using national health insurance claims data. (2) Methods: A total of 43,848 patients who started tamoxifen therapy between 2015 and 2020 and had no prior ophthalmic diseases or other conditions requiring screening for retinopathy were included. The annual numbers of tamoxifen users and new initiators of tamoxifen therapy were assessed. The screening examinations were separated into baseline (first ophthalmic examination after tamoxifen administration) and subsequent monitoring examinations. The timing and modalities for the baseline and subsequent monitoring examinations performed between 2015 and 2021 were assessed in tamoxifen users. (3) Results: The annual number of tamoxifen users increased over the study period from 54,056 in 2015 to 81,720 in 2021. The number of patients who underwent ophthalmic examination after tamoxifen administration was 8961 (20.4%). Baseline screening was performed in 6.5% of patients within 1 year of use, and subsequent monitoring was performed in 27.8% of patients who underwent baseline screening. Funduscopy or fundus photography was performed most commonly for baseline screening and subsequent monitoring (99.0% and 98.6%, respectively), while optical coherence tomography was performed only in 21.9% and 29.6% of baseline and monitoring examinations, respectively. The average number of monitoring examinations per year was 0.68 ± 0.45. Although the annual percentage of patients receiving a baseline examination within 1 year gradually increased over time, the percentage of those with subsequent monitoring performed within 1 year was similar over the study period. (4) Conclusions: Our finding, appropriate screening in a small proportion of patients receiving tamoxifen, suggests the need to promote awareness among healthcare professionals and develop a standardized approach for screening for tamoxifen retinopathy.

Multi-walled carbon nanotube (MWCNT) exposure was observed to cause damages on the viability of ocular cells, however, the underlying mechanisms remain not well understood. Epigenetic alterations that regulate gene expression have been identified as a major responsiveness to environmental challenge. Thus, the aim of this study was to screen methylation-regulated genes involved in MWCNT exposure. The Illumina Human Methylation 850 K array was employed to determine the genome-wide DNA methylation profile of human retinal pigment epithelial cell line (ARPE-19) exposed to 50% inhibition concentration of MWCNTs (100 μg/ml) for 24 h or without (n = 3 for each group). Then, the transcriptome data obtained by high-throughput RNA sequencing previously were integrated with DNA methylome to identify the overlapped genes. As a result, the integrative bioinformatics analysis identified that compared with controls, FA complementation group C (FANCC) was hypermethylated and downregulated in MWCNT-exposed ARPE-19 cells. Quantitative real-time polymerase chain reaction analysis confirmed the mRNA expression level of FANCC was significantly decreased following MWCNT treatment and the addition of DNA methylation inhibitor 5-Aza-deoxycytidine (10 μM) reversed this decrease. Pyrosequencing analysis further validated the hypermethylation status at the 5\'-untranslated promoter region of FANCC (cg14583550) in MWCNT-exposed ARPE-19 cells. Protein-protein interaction network and function analyses predicted that FANCC may contribute to MWCNT-induced cytotoxicity by interacting with heat shock protein 90 beta family member 1 and then upregulating cytokine interleukin-6 and apoptosis biomarker caspase 3. In conclusion, the present study links the epigenetic modification of FANCC with the pathogenesis of MWCNT-induced retinal toxicity.

Purpose: To present a case of a chemotherapy regimen combining a fibroblast growth factor receptor (FGFR) and mitogen-activated protein kinase kinase (MEK) inhibitor leading to serous retinopathy. Methods: A retrospective chart review of a single case was performed. Results: A 67-year-old man with pancreatic and prostate cancer developed bilateral multifocal pockets of subretinal fluid while on an experimental chemotherapy regimen combining an MEK inhibitor (trametinib) and an FGFR inhibitor (erdafitinib). Conclusions: Given that FGFR lies upstream to the mitogen-activated protein kinase signaling pathway, retinal toxicity may be more severe and more common with FGFR-MEK combination therapy. Future studies are necessary to guide ophthalmic surveillance.

OBJECTIVE: To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used.
METHODS: Population-based cohort study.
METHODS: For evaluation of nationwide usage, 133 762 individuals who received PPS prescriptions between 2012 and 2021 were included. To investigate practice patterns, 55 487 individuals (referred to as overall users) who initiated PPS therapy between 2018 and 2020 were identified using the Health Insurance Review and Assessment database. After excluding patients with ophthalmic diseases before PPS administration, 34 857 PPS users without prior ophthalmic diseases were identified.
METHODS: Ophthalmic examinations performed after initiating PPS therapy were categorized as baseline and subsequent monitoring examinations. The timing and modalities employed for these examinations were analyzed. The annual trends in PPS utilization and maculopathy screening were evaluated by assessing the number of PPS users and determining the proportion of patients receiving retinal/macular examinations among these users.
METHODS: Performance of baseline and subsequent monitoring examinations and timing and modalities used for screening.
RESULTS: The number of PPS users dramatically increased annually over the study period from 5494 in 2012 to 40 451 in 2021. However, the majority of PPS users did not undergo baseline or subsequent monitoring examinations for PPM. Only 27.2% and 12.4% of PPS users without prior ophthalmic disease underwent baseline and monitoring examinations, respectively. Funduscopy/fundus photography was the most commonly utilized, whereas OCT and fundus autofluorescence (FAF) were performed in only 45.2% and 5.3% of the PPS users without prior ophthalmic diseases for monitoring, respectively. The performance of the screening examinations differed significantly across the 3 different daily dose and duration groups (all P < 0.05).
CONCLUSIONS: This study highlights the lack of performance of baseline and monitoring examinations for maculopathy in most patients taking PPS in South Korea. The limited use of OCT and FAF suggests potential insensitivity in detecting PPM. These findings emphasize the need for improvements in screening practices, including increased awareness and referrals to ophthalmologists, utilization of more sensitive modalities, and regular monitoring to enable early detection of PPM.
BACKGROUND: The authors have no proprietary or commercial interest in any materials discussed in this article.

UNASSIGNED: To report the structural and functional changes in a 67-year-old male with pentosan polysulfate sodium (PPS) maculopathy with a progressive resolution of bilateral vitelliform lesions after PPS cessation.
UNASSIGNED: The patient was initially seen after taking daily PPS for over 26 years. Three months after discontinuing PPS, the bilateral vitelliform lesions identified on spectral-domain optical coherence tomography (SD-OCT) at initial consultation had completely resolved. Bilateral resolution of vitelliform lesions was associated with a decline in best-corrected visual acuity, and ellipsoid zone disruption on SD-OCT.
UNASSIGNED: Several PPS maculopathy phenotypes have been previously described including vitelliform lesions. Our case highlights that discontinuing PPS may lead to rapid resolution of vitelliform lesions in PPS maculopathy and may be associated with a rapid reduction in vision.

UNASSIGNED: To explore the retinal toxicity of pharmaceuticals and personal care products (PPCPs), flame retardants, bisphenols, phthalates, and polycyclic aromatic hydrocarbons (PAHs) on human retinal progenitor cells (RPCs) and retinal pigment epithelial (RPE) cells, which are the primary cell types at the early stages of retinal development, vital for subsequent functional cell type differentiation, and closely related to retinal diseases.
UNASSIGNED: After 23 days of differentiation, human embryonic stem cell (hESC)-based retinal pre-organoids, containing RPCs and RPE cells, were exposed to 10, 100, and 1000 nM pesticides (butachlor, terbutryn, imidacloprid, deltamethrin, pendimethalin, and carbaryl), flame retardants (PFOS, TBBPA, DBDPE, and TDCIPP), PPCPs (climbazole and BHT), and other typical pollutants (phenanthrene, DCHP, and BPA) for seven days. Then, mRNA expression changes were monitored and compared.
UNASSIGNED: (1) The selected pollutants did not show strong effects at environmental and human-relevant concentrations, although the effects of flame retardants were more potent than those of other categories of chemicals. Surprisingly, some pollutants with distinct structures showed similar adverse effects. (2) Exposure to pollutants induced different degrees of cell detachment, probably due to alterations in extracellular matrix and/or cell adhesion.
UNASSIGNED: In this study, we established a retinal pre-organoid model suitable for evaluating multiple pollutants\' effects, and pointed out the potential retinal toxicity of flame retardants, among other pollutants. Nevertheless, the potential mechanisms of toxicity and the effects on cell detachment are still unclear and deserve further exploration. Additionally, this model holds promise for screening interventions aimed at mitigating the detrimental effects of these pollutants.