Long-term use of hydroxychloroquine can cause retinopathy, which may result in severe and progressive visual loss. In the past decade, hydroxychloroquine use has markedly increased and modern retinal imaging techniques have enabled the detection of early, pre-symptomatic disease. As a consequence, the prevalence of retinal toxicity in long-term hydroxychloroquine users is known to be higher than was previously estimated. The pathophysiology of the retinopathy is incompletely characterised, although significant advances have been made in understanding the disease from clinical imaging studies. Hydroxychloroquine retinopathy elicits sufficient public health concern to justify the implementation of retinopathy screening programs for patients at risk. Here, we describe the historical background of hydroxychloroquine retinopathy and summarize its current understanding. We review the utility and limitations of each of the mainstream diagnostic tests used to detect hydroxychloroquine retinopathy. The key considerations towards a consensus on the definition of hydroxychloroquine retinopathy are outlined in the context of what is known of the natural history of the disease. We compare the current screening recommendations for hydroxychloroquine retinopathy, identifying where additional evidence is required, and the management of proven cases of toxicity. Finally, we highlight the areas for further investigation, which may further reduce the risk of visual loss in hydroxychloroquine users.

Alteration of retinal angiogenesis during development leads to retinopathy of prematurity (ROP) in preterm infants, which is a leading cause of visual impairment in children. A number of clinical studies have reported higher rates of ROP in infants who had perinatal infections or inflammation, suggesting that exposure of the developing retina to inflammation may disturb retinal vessel development. Thus, we investigated the effects of systemic inflammation on retinal vessel development and retinal inflammation in neonatal rats. To induce systemic inflammation, we intraperitoneally injected 100 μl lipopolysaccharide (LPS, 0.25 mg/ml) or the same volume of normal saline in rat pups on postnatal days 1, 3, and 5. The retinas were extracted on postnatal days 7 and 14, and subjected to assays for retinal vessels, inflammatory cells and molecules, and apoptosis. We found that intraperitoneal injection of LPS impaired retinal vessel development by decreasing vessel extension, reducing capillary density, and inducing localized overgrowth of abnormal retinal vessels and dilated peripheral vascular ridge, all of which are characteristic findings of ROP. Also, a large number of CD11c⁺ inflammatory cells and astrocytes were localized in the lesion of abnormal vessels. Further analysis revealed that the number of major histocompatibility complex (MHC) class II^loCD68^loCD11b^loCD11c^hi cells in the retina was higher in LPS-treated rats compared to controls. Similarly, the levels of TNF-α, IL-1β, and IL-12a were increased in LPS-treated retina. Also, apoptosis was increased in the inner retinal layer where retinal vessels are located. Our data demonstrate that systemic LPS-induced inflammation elicits retinal inflammation and impairs retinal angiogenesis in neonatal rats, implicating perinatal inflammation in the pathogenesis of ROP.

Importance: Practice patterns of hydroxychloroquine retinopathy screening have not yet been reported at a national level in South Korea.Objective: To investigate the practice patterns of timing and modality for hydroxychloroquine retinopathy screening in South Korea.Design, Setting, and Participants: This nationwide population-based cohort study of patients in South Korea used data from the national Health Insurance Review and Assessment database. Patients at risk were identified as those who had initiated hydroxychloroquine therapy between January 1, 2009, and December 31, 2020, and used it for 6 months or more. Patients were excluded if they underwent any of the 4 screening modalities recommended by the American Academy of Ophthalmology (AAO) for other ophthalmic diseases prior to hydroxychloroquine use. The timing and modalities of screening used in baseline and monitoring examinations were assessed between January 1, 2015, and December 31, 2021, among patients at risk and long-term (≥5 years) users.Exposure: Adherence of baseline screening practices to the 2016 AAO recommendations (fundus examination within 1 year of drug use) was evaluated; adherence of monitoring examinations in year 5 was classified as appropriate (≥2 tests recommended by the AAO), unscreened (no test performed), and underscreened (insufficient number of tests).Main Outcomes and Measures: Timing of screening and modalities used at baseline and monitoring examinations.Results: A total of 65 406 patients at risk (mean [SD] age, 53.0 [15.5] years; 50 622 women [77.4%]) were included; 29 776 patients were long-term users (mean [SD] age, 50.1 [14.7] years; 24 898 women [83.6%]). Baseline screening was performed for 20.8% of the patients within 1 year, with a gradual increase from 16.6% in 2015 to 25.6% in 2021. Monitoring examinations, mostly using optical coherence tomography and/or visual field tests, were performed for only 13.5% of the long-term users in year 5 and for 31.6% of the long-term users after 5 years. Appropriate monitoring was performed for less than 10% of long-term users each year from 2015 to 2021; however, the percentage gradually increased over time. The percentage of patients undergoing any monitoring examination in year 5 was 2.3 times greater for those who had received baseline screening than for those who did not (27.4% vs 11.9%; P < .001).Conclusions and Relevance: This study suggests there is an improving trend in retinopathy screening among hydroxychloroquine users in South Korea; however, most long-term users remained unscreened after 5 years of use. Baseline screening may be useful in reducing the number of unscreened long-term users.

The advent of smartphone fundus imaging technology has marked a significant evolution in the field of ophthalmology, offering a novel approach to the diagnosis and management of retinopathy. This review provides an overview of smartphone fundus imaging, including clinical applications, advantages, limitations, clinical applications, and future directions. The traditional fundus imaging techniques are limited by their cost, portability, and accessibility, particularly in resource-limited settings. Smartphone fundus imaging emerges as a cost-effective, portable, and accessible alternative. This technology facilitates the early detection and monitoring of various retinal pathologies, including diabetic retinopathy, age-related macular degeneration, and retinal vascular disorders, thereby democratizing access to essential diagnostic services. Despite its advantages, smartphone fundus imaging faces challenges in image quality, standardization, regulatory considerations, and medicolegal issues. By addressing these limitations, this review highlights the areas for future research and development to fully harness the potential of smartphone fundus imaging in enhancing patient care and visual outcomes. The integration of this technology into telemedicine is also discussed, underscoring its role in facilitating remote patient care and collaborative care among physicians. Through this review, we aim to contribute to the understanding and advancement of smartphone fundus imaging as a valuable tool in ophthalmic practice, paving the way for its broader adoption and integration into medical diagnostics.