Hydroxychloroquine Retinopathy Research Articles

Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes

ImportanceThe major toxic effect of hydroxychloroquine is retinopathy. Thus, current guidelines recommend limiting the dose and screening annually for retinopathy among all long-term users, but individual patient factors may be associated with retinopathy risk.ObjectiveTo identify risk factors beyond hydroxychloroquine dose and duration of use for hydroxychloroquine retinopathy.Design, Setting, and ParticipantsThis cohort study of 4677 patients in the Kaiser Permanente Northern California integrated health network who initiated hydroxychloroquine, continued treatment, and underwent retinopathy screening after 5 years of use was conducted from July 1, 1997, to December 31, 2020, with up to 15 years of follow-up. Statistical analysis was performed in August 2023.ExposureCandidate risk factors included age at hydroxychloroquine initiation, sex, race and ethnicity, indications, chronic kidney disease (CKD), liver disease, diabetes, tamoxifen use, and medications that interact with hydroxychloroquine metabolism. Hydroxychloroquine dose was assessed from pharmacy dispensing records.Main Outcome and MeasuresIncident hydroxychloroquine retinopathy was adjudicated from masked review of guideline-recommended screening studies and classified as parafoveal or pericentral pattern. Multivariable Cox proportional hazards regression was used to assess potential risk factors for hydroxychloroquine retinopathy within 15 years of initiation.ResultsOf 4677 long-term hydroxychloroquine users (mean [SD] age at initiation, 52.4 [14.1] years; 3877 women [82.9%]), 125 patients developed hydroxychloroquine retinopathy within 15 years (102 parafoveal, 23 pericentral). Older age at time of hydroxychloroquine initiation was associated with retinopathy risk, with adjusted hazard ratios (HRs) of 2.48 (95% CI, 1.28-4.78) for those aged 45 to 54 years, 3.82 (95% CI, 2.05-7.14) for those aged 55 to 64 years, and 5.68 (95% CI, 2.99-10.79) for those aged 65 years or older compared with those younger than 45 years. The risk of retinopathy was higher among females than males (HR, 3.83 [95% CI, 1.86-7.89]), among patients with CKD stage 3 or greater (HR, 1.95 [95% CI, 1.25-3.04]), and among individuals with tamoxifen use (HR, 3.43 [95% CI, 1.08-10.89]). The likelihood of pericentral retinopathy was higher among Asian patients (HR, 15.02 [95% CI, 4.82-46.87]) and Black patients (HR, 5.51 [95% CI, 1.22-24.97]) compared with non-Hispanic White patients.Conclusions and RelevanceThis study suggests that increasing age, female sex, CKD stage 3 or greater, and tamoxifen use were associated with a higher risk of hydroxychloroquine retinopathy, whereas being younger than 45 years at hydroxychloroquine initiation and male sex were associated with a lower risk. Race and ethnicity were also associated with the pattern of retinopathy. These factors should be incorporated into hydroxychloroquine dosing decisions.

Exome sequencing and genome-wide association analyses unveils the genetic predisposition in hydroxychloroquine retinopathy.

To unveil the candidate susceptibility genes in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy using whole exome sequencing (WES) and genome-wide association study (GWAS). Patients with a diagnosis of CQ/HCQ retinopathy based on the comprehensive demographic and ocular examination were included. The peripheral blood was extracted for WES and GWAS analyses. The Chinese Han Southern database from 1000 genomes was used as control group to compare the affected percentage. Multivariate logistic regression analysis adjusted for age, HCQ dose, duration and renal disease were used to analyze the correlation between genetic variants and visual outcome. A poor vision outcome was defined as visual acuity <6/12. An abnormal anatomical outcome was defined as disruption of ellipsoid zone in the fovea. Twenty-nine patients with an average age of 60.9 ± 13.4 years, treatment duration of 12.1 ± 6.2 years, daily dose of 8.5 ± 4.1 mg/kg, and the cumulative dose of 1637.5 ± 772.5 g, were genotyped. Several candidate genes associated with CQ/HCQ retinopathy were found, including RP1L1, RPGR and RPE65, with a difference of affected percentage over 50% in mutation between the case and control groups. New foci in CCDC66: rs56616026 (OR = 63.43, p = 1.63 × 10-8) and rs56616023 (OR = 104.7, p = 5.02 × 10-10) were identified significantly associated with HCQ retinopathy. Multivariate analysis revealed increased genetic variants were significantly associated with poor functional (OR = 1.600, p = 0.004) and structural outcome (OR = 1.318, p = 0.043). Several candidate susceptibility genes including RP1L1, RPGR, RPE65 and CCDC66 were identified to be associated with CQ/HCQ retinopathy. In addition to disease susceptibility, patients with increased genetic variants are more vulnerable to poor visual outcomes.

Dermatologists' and Rheumatologists' Adherence to the Latest Recommendations for Screening of Hydroxychloroquine Retinopathy in Saudi Arabia: A Cross-Sectional Study.

Hydroxychloroquine (HCQ) is used to manage the symptoms of inflammatory rheumatic and dermatologic disorders. However, HCQ retinopathy is aserious side effect becauseeven after the drug is discontinued, irreversible vision loss may occur and may continue to progress.According to the American Academy of Ophthalmology (AAO),the recent recommendation for HCQ dosing is ≤5 mg/kg of real body weight, with baseline ophthalmologic screening during the first year of HCQ treatment and yearly screening after five years of continuous use of HCQ medication, unless the patient is at high risk or symptoms have developed.Nonetheless, this study aims to assess dermatologists' and rheumatologists' adherence in Saudi Arabia to the 2016 AAO HCQ retinal toxicity guidelines. A questionnaire-based cross-sectional study was conducted on dermatologists and rheumatologists in Saudi Arabia. It was conducted between August and September 2022 and questionnaires were sent to dermatologists and rheumatologists via their professional emails or accounts. The collected sample consisted of 635 participants; males and females represented 54% and 46%, respectively; 47.6% were consultants; 50.1% were rheumatologists; and 49.9% were dermatologists. Approximately 28.2% of the participants reported treating one to three patients with HCQ in the previous year. Only 45.4% of the respondents stated that the ideal recommended HCQ dose for reducing the risk of retinopathy is "≤ 5 mg/kg of the real body weight." More than 50% of the respondents stated that systemic lupus erythematosus was the most common disease for which they used HCQ. Additionally, 36.5% of the physicians screened patients during the first year of HCQ treatment. We found significant associations between practice levels and specialty practice-related questions with a p-value of less than 0.05, except for the specialty practice-related question, "What is the most common disease for which you use HCQ?" with a p-value of 0.074. Also, we found significant associations between all demographic variables and screening-related variables with a p-value of less than 0.05, with two exceptions: no significant associations were found between specialty area and the screening-related question, "Do you recommend screening tests for all patients starting treatment with HCQ?" at p = 0.270, and gender and the screening-related question, "When would you recommend screening tests for a patient without risk?" at p = 0.142. Dermatologists and rheumatologists in Saudi Arabia have shown poor adherence to the most recent AAO recommendations. Educating physicians and patients about the AAO guidelines is needed for HCQ to be used in a way that is both effective and safe.

Screening Practices and Late Diagnosis of Hydroxychloroquine Retinopathy in Asian Patients.

To investigate the associations between screening practices and late diagnosis in Asian patients with hydroxychloroquine retinopathy. In total, 92 Korean patients with hydroxychloroquine retinopathy were included and separated into late diagnosis and earlier diagnosis groups according to the retinopathy stage at the time of diagnosis. Details of screening practices regarding timing and modalities for baseline and annual monitoring examinations were compared between the two groups. Adherence to the current American Academy of Ophthalmology (AAO) guidelines was compared between the two groups. Timing of baseline and initial monitoring examinations was appropriate as per the AAO guidelines in only 5.3% of patients with late diagnosis. There were significant differences in the proportions of patients receiving initial monitoring at 5 years of use and those receiving annual monitoring between the late and earlier diagnosis groups (P=0.003 and <0.001, respectively). The duration from the start date of hydroxychloroquine therapy to the first monitoring examination was significantly prolonged in the late diagnosis group (P<0.001). Multivariate logistic regression revealed significant association of the time duration to the first monitoring exam (P=0.042) and age (P=0.028) with late diagnosis. Our results suggest that poor adherence to the AAO guideline, particularly delayed initial monitoring, may be associated with late diagnosis of hydroxychloroquine retinopathy.

Systematic hydroxychloroquine retinopathy monitoring programme: cost benefit comparing to a hospital-based system.

Systematic hydroxychloroquine retinopathy monitoring programme: cost benefit comparing to a hospital-based system.

Identification of new risk factors for hydroxychloroquine and chloroquine retinopathy in systemic lupus erythematosus patients

BackgroundLong-term hydroxychloroquine (HCQ) or chloroquine (CQ) intake causes retinal toxicity in 0.3–8 % of patients with rheumatic diseases. Numerous risk factors have been described, eg, daily dose by weight, treatment duration, chronic kidney disease, concurrent tamoxifen therapy and pre-existing retinal or macular disease. However, those factors cannot explain the entire risk of developing antimalarial retinopathy. ObjectiveThis study was undertaken to identify new risk factors associated with HCQ or CQ retinopathy (QRNP) in systemic lupus erythematosus (SLE) patients. MethodsThis case–control (1:2) study compared SLE patients with QRNP (cases) to those without (controls). Controls were matched for sex and known QRNP risk factors: HCQ and/or CQ treatment duration (±1 year) and age (±5 year) at SLE diagnosis. ResultsForty-eight cases were compared to 96 SLE controls. Multivariable logistic-regression analysis retained the following as independent determinants significantly associated with QRNP: concomitant selective serotonin-reuptake inhibitor (SSRI) or serotonin- and norepinephrine-reuptake inhibitor (SNRI) intake (OR [95 % confidence interval] 6.6 [1.2 to 40.9]; p < 0.01); antiphospholipid syndrome (OR=8.9 [2.2 to 41.4] p < 0.01); blood hydroxychloroquine/desethylchloroquine concentration ([HCQ]/[DCQ]) ratio <7.2 (OR 8.4 [2.7 to 30.8]; p < 0.01) or skin phototype ≥4 (OR 5.5 [1.4 to 26.5]; p = 0.02), but not daily HCQ dose, blood [HCQ] or body mass index. ConclusionThe results of this case–control study identified blood [HCQ]/[DCQ] ratio, concurrent SSRI/SNRI therapy, skin phototype ≥4 and antiphospholipid syndrome as new risk factors for QRNP.

Demographic and clinical characteristics associated with screening practices for hydroxychloroquine retinopathy

In this nationwide population-based cohort study, we investigated the demographic and clinical characteristics associated with hydroxychloroquine retinopathy screening using the National Health Insurance Review and Assessment database in South Korea. This study included a total of 32,732 at-risk patients, identified based on having been prescribed hydroxychloroquine for at least 6 months, and 15,477 long-term (> 5 years) users between January 2010 and December 2020. Participants were categorized based on the performance of baseline examinations (within 1 year of hydroxychloroquine use) and monitoring examinations (after 5 years of hydroxychloroquine use). Demographic and clinical factors, including hospitals and medical specialties prescribing hydroxychloroquine, indications for hydroxychloroquine use, and prescription details, were compared between groups. Significant differences were found in sex, residence, departments and hospitals (primary vs. referral centers) where hydroxychloroquine was prescribed, diagnosis for hydroxychloroquine therapy, and mean daily dose between patients who did and did not undergo baseline or monitoring examinations (all P < 0.01). Patients who received hydroxychloroquine prescriptions from referral hospitals were more likely to undergo baseline and monitoring examinations compared to those from primary clinics (both P < 0.001). Additionally, patients who received hydroxychloroquine prescriptions from the rheumatology department and had systemic lupus erythematosus were more likely to undergo baseline and monitoring examinations compared to other patients (all P < 0.001). There were notable differences in the number of modalities used for retinopathy screening between primary and referral centers (P < 0.001). Our findings suggest that several clinical factors related to hydroxychloroquine prescription and screening centers are associated with retinopathy screening practices.

10-2 Visual Field for Detecting Early Hydroxychloroquine Retinopathy

10-2 Visual Field for Detecting Early Hydroxychloroquine Retinopathy

Effects of hydroxychloroquine therapy on choroidal volume and choroidal vascularity index.

To determine changes in choroidal volume (CV) and choroidal vascularity index (CVI) in patients on hydroxychloroquine (HCQ) therapy. Retrospective analysis of patients on HCQ therapy. CV and CVI were assessed below the central foveal region on spectral-domain optical coherence tomography using an automatic denoising and localization algorithm. CV and CVI were compared with age-matched controls. Regression analyses were performed to generate associations between CV and CVI with demographics and HCQ treatment parameters. Associations were assessed using a generalized estimating equation model adjusted for intra-subject inter-eye correlations. A total of 137 adult patients (23 males and 114 females) were included. Mean age was 45.6 ± 13.7 years and most patients identified as Caucasian (79%). Total duration of HCQ therapy ranged from 3 months to 20 years. Daily HCQ intake varied from 150-600 mg (mean = 304 mg), while cumulative doses ranged from 18-2,800 g. At presentation, the median CV was 0.51 (IQR:0.356-0.747) mm, and median CVI was 0.559 (IQR:0.528-0.578). Increased cumulative HCQ dose was associated with decreased CV (p = 0.006). Compared to age-matched controls, CV, CVI, and luminal area were significantly lower in the study group (p = 0.0003, 0.0001, and 0.0002). In this study, we present a novel analysis of key biomarkers which predate the occurrence of HCQ retinopathy. Choroidal volume and vascularity index are significantly reduced in patients on HCQ therapy, especially at higher cumulative doses. These findings suggest new tools to guide medical decision-making for patients receiving HCQ therapy for rheumatologic diseases.

Causes and trends of late diagnosis in Korean patients with hydroxychloroquine retinopathy.

Late diagnosis of hydroxychloroquine retinopathy remains a major concern, with the potential for irreversible visual impairment. This study aimed to investigate the causes of late diagnosis in a hospital-based cohort of Korean patients with hydroxychloroquine retinopathy and assess the trend of late diagnosis from 2015 to 2022. Thirty-eight patients with a late diagnosis (severe stage at diagnosis) among 94 patients with hydroxychloroquine retinopathy were included in the analysis. The causes of late diagnosis were categorized as referral-related, patient-related, and screening-related factors. The most prevalent cause was no or late referral to ophthalmologists, contributing to a significant gap in timely identification. Patient-related causes included delayed monitoring visits despite scheduled appointments and early-onset disease. Screening-related causes encompassed an insufficient number of sensitive tests, leading to inadequate evidence for diagnosis, and missed or wrong diagnoses by screening physicians. The proportion of late diagnoses decreased over time, indicating improvements in overall screening and detection. The decreasing proportions of screening-related causes suggest advancements in screening practices and the use of multiple sensitive tests for screening. Efforts to further reduce late diagnoses and improve screening and diagnostic processes are necessary. Our data emphasize the importance of timely referral to ophthalmologists for early detection and management.

Evaluation of Retinal Toxicity by SD-OCT due to Long-Term Exposure to Hydroxycholorquine among Rheumatoid Arthritis Patients

Background Hydroxychloroquine is used increasingly in the management of a variety of autoimmune disorders, with well-established roles in dermatology and rheumatology and emerging roles in oncology. However, Hydroxychloroquine and chloroquine (CQ) have been associated with irreversible visual loss due to retinal toxicity. Cessation of the use of hydroxychloroquine at an early stage of damage might prevent functional loss; however, after maculopathy has developed, cessation of the drug does not show clinical recovery. Because discontinuation of Therapy may reverse retinal toxicity, early detection of toxicity changes is vitally important. Objective to evaluate the involvement of retina in hydroxychloroquine (HCQ) retinopathy among rheumatoid arthritis patients using data from spectral domain optical coherence tomography (SDOCT) and to correlate toxicity with dose, duration of use and cumulative effect of HCQ. Patients and Methods Cross sectional Study. In total 13 patients (26 eyes) attending the rheumatological outpatient clinic of El Demerdash hospital, from October 2019 to February 2020 were enrolled in the study after the approval of the research ethical committee in the Faculty of Medicine, Ain Shams University. A full history was taken from the patients and full ophthalmological examination was done. In our study we perform OCT for all patients by using the Nidek RS-3,000 Advance SD-OCT with the “Macula Map” protocol that imaged a 6 × 6 mm area with 64 raster B-scans, each composed of 1024 A-scans. Results The study showed that was highly significant negative correlation between duration of exposure and CMT (p-value =0.008) and highly significant negative correlation between cumulative dose and CMT (p-value =0.005). Also, there was statistically significant negative correlation between age and thickness of inner and outer nasal quadrant (p-value= 0.015, p-value= 0.001) respectively and between age and inner and outer superior quadrant (p-value= 0.048, p-value= 0.000) respectively, in ETDRS thickness map. It also found statistically significant negative correlation between daily dose and thickness of outer nasal quadrant of thickness map (p-value= 0.045). Conclusion The present study show the presence / absence of retinal toxicity in rheumatoid arthritis patients use hydroxychloroquine for 5years or more using SD-OCT and found a statistically significant negative correlation between central macular thickness and cumulative dose of HCQ and between central macular thickness and duration of HCQ use.

Detection of Hydroxychloroquine Retinopathy via Hyperspectral and Deep Learning through Ophthalmoscope Images.

Hydroxychloroquine, also known as quinine, is primarily utilized to manage various autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. However, this drug has side effects, including diarrhea, blurred vision, headache, skin itching, poor appetite, and gastrointestinal discomfort. Blurred vision is caused by irreversible retinal damages and can only be mitigated by reducing hydroxychloroquine dosage or discontinuing the drug under a physician's supervision. In this study, color fundus images were utilized to identify differences in lesions caused by hydroxychloroquine. A total of 176 color fundus images were captured from a cohort of 91 participants, comprising 25 patients diagnosed with hydroxychloroquine retinopathy and 66 individuals without any retinopathy. The mean age of the participants was 75.67 ± 7.76. Following the selection of a specific region of interest within each image, hyperspectral conversion technology was employed to obtain the spectrum of the sampled image. Spectral analysis was then conducted to discern differences between normal and hydroxychloroquine-induced lesions that are imperceptible to the human eye on the color fundus images. We implemented a deep learning model to detect lesions, leveraging four artificial neural networks (ResNet50, Inception_v3, GoogLeNet, and EfficientNet). The overall accuracy of ResNet50 reached 93% for the original images (ORIs) and 96% for the hyperspectral images (HSIs). The overall accuracy of Inception_v3 was 87% for ORIs and 91% for HSI, and that of GoogLeNet was 88% for ORIs and 91% for HSIs. Finally, EfficientNet achieved an overall accuracy of 94% for ORIs and 97% for HSIs.

Use of optical coherence tomography retinal thickness deviation map for hydroxychloroquine retinopathy screening

Background: Hydroxychloroquine (HCQS) is widely used to treat several rheumatic and skin diseases and can cause damage to the outer retina, known as HCQS retinopathy, and is common among long-term users of the drug with higher daily dose by weight. The goal of screening for retinopathy is to recognize signs of toxicity at an early enough stage to prevent the loss of visual acuity. Aims and Objectives: This study aimed to evaluate the diagnostic performance of a commercially available retinal thickness deviation map obtained by spectral-domain (SD) optical coherence tomography (OCT) for screening of HCQS retinopathy. Materials and Methods: This study was a prospective comparative study between unaffected (patients who did not develop retina toxicity) and affected (who developed toxicity) of 50 patients of the age group of 14–60 years taking HCQS medication for several dermatological and rheumatologic disorders. The patients who fulfilled the inclusion criteria were screened for HCQS retinal toxicity using SD-OCT, standard automated perimetry, fundus autofluorescence, and comprehensive ophthalmic examinations. Results: In this study, in group 2 patients, 60% were having parafoveal, 30% having perifoveal, and 10% having a mixed pattern (P&lt;0.001) of HCQS retinopathy, and the mean deviation and pattern standard deviation increase as the severity of disease increases (P&lt;0.005). Conclusion: This study concluded that HCQS is a safer drug and can be used safely in these patients with proper HCQS retinal toxicity monitoring with an SD-OCT-generated retinal thickness deviation map and with regular follow-up to monitor reduced thickness in the parafoveal region.

Unmet needs and future perspectives in hydroxychloroquine retinopathy.

Retinopathy is a well-recognized toxic effect of hydroxychloroquine treatment. As hydroxychloroquine retinopathy is potentially a vision-threatening condition, early detection is imperative to minimize vision loss due to drug toxicity. However, early detection of hydroxychloroquine retinopathy is still challenging even with modern retinal imaging techniques. No treatment has been established for this condition, except for drug cessation to minimize further damage. In this perspective article, we aimed to summarize the knowledge gaps and unmet needs in current clinical practice and research in hydroxychloroquine retinopathy. The information presented in this article may help guide the future directions of screening practices and research in hydroxychloroquine retinopathy.

Hydroxychloroquine-induced Retinal Toxicity.

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.

Practice Patterns of Screening for Hydroxychloroquine Retinopathy in South Korea

Practice patterns of hydroxychloroquine retinopathy screening have not yet been reported at a national level in South Korea. To investigate the practice patterns of timing and modality for hydroxychloroquine retinopathy screening in South Korea. 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. 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). Timing of screening and modalities used at baseline and monitoring examinations. 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). 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.

Review of Retinal Imaging Modalities for Hydroxychloroquine Retinopathy.

This review provides an overview of conventional and novel retinal imaging modalities for hydroxychloroquine (HCQ) retinopathy. HCQ retinopathy is a form of toxic retinopathy resulting from HCQ use for a variety of autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Each imaging modality detects a different aspect of HCQ retinopathy and shows a unique complement of structural changes. Conventionally, spectral-domain optical coherence tomography (SD-OCT), which shows loss or attenuation of the outer retina and/or retinal pigment epithelium-Bruch's membrane complex, and fundus autofluorescence (FAF), which shows parafoveal or pericentral abnormalities, are used to assess HCQ retinopathy. Additionally, several variations of OCT (retinal and choroidal thickness measurements, choroidal vascularity index, widefield OCT, en face imaging, minimum intensity analysis, and artificial intelligence techniques) and FAF techniques (quantitative FAF, near-infrared FAF, fluorescence lifetime imaging ophthalmoscopy, and widefield FAF) have been applied to assess HCQ retinopathy. Other novel retinal imaging techniques that are being studied for early detection of HCQ retinopathy include OCT angiography, multicolour imaging, adaptive optics, and retromode imaging, although further testing is required for validation.

Nationwide patterns of hydroxychloroquine dosing and monitoring of retinal toxicity in patients with systemic lupus erythematosus

This study identified trends in hydroxychloroquine (HCQ) prescription and retinopathy screening in patients with systemic lupus erythematosus (SLE) according to clinical practice guidelines to minimise the risk of HCQ retinopathy. We used data from patients diagnosed with SLE between 2004 and 2019 from the National Health Insurance Service in Korea. To assess trends of daily dose per actual body weight (ABW), we performed an interrupted time-series analysis and identified effects after revision of guidelines. Among 38,973 patients with SLE, 28,415 (72.9%) were prescribed HCQ from 2004 to 2019. The proportion of patients using HCQ among SLE patients was 63% in 2004 and increased to 76% in 2019. The median daily dose per ABW for HCQ users decreased from 5.88 mg/kg in 2004 to 3.98 mg/kg in 2019, and from 5.45 mg/kg in 2005 to 4.17 mg/kg in 2019 for HCQ new users. The annual implementation rate of screening tests among HCQ new users increased from 3.5% in 2006 to 22.5% in 2019. Study results indicated that HCQ dosing management was adequate based on the revised guidelines. Although the implementation rate of retinal screening has increased, it is necessary to enhance awareness of retinal screening in clinical settings.

P052 Hydroxychloroquine retinopathy incidence in a UK specialist centre: a machine learning/natural language processing pilot study

Abstract Background/Aims Hydroxychloroquine (HCQ) is an antimalarial drug commonly used in autoimmune conditions such as systemic lupus erythematous (SLE) and rheumatoid arthritis (RA). In SLE, it has been shown to significantly improve survival and morbidity, but is known to be rarely associated with sight-threatening retinopathy. Data from the US suggested HCQ retinopathy was significantly more common than previously thought (up to 7%), causing the Royal College of Ophthalmology to recommend increased screening in 2018. Natural language processing (NLP) is a machine learning technique which purports to be able to identify patients with a specific diagnosis or taking specific mediations from unstructured data such as clinic letters. This study aimed to understand whether NLP could be used to (i) identify patients taking HCQ and (ii) determine rates of HCQ retinopathy from clinic letters in a UK tertiary Rheumatology centre. Methods The study was set across the Kellgren Centre for Rheumatology (regional tertiary lupus centre) and the Manchester Eye Hospital. Analysis was performed using CogStack/MedCat, an open source self-supervised NLP framework which extracts SNOMED coded items from unstructured electronic health data such as clinic letters. All clinical documents 2012-2022 were identified for patients attending clinics coded as HCQ retinopathy screening. These were processed through Cogstack/MedCat in two stages. Firstly, it identified all patients exposed to HCQ according to their clinic letters. Subsequently, MedCat searched all clinical documents for those patients for references to HCQ retinopathy, HCQ retinopathy screening or retinopathy. Diabetic retinopathy was used to sense-check for other forms of retinopathy. Finally, manual validation of the HCQ retinopathy positive cases was performed. Results From an original 202,704 documents, HCQ exposure was identified in 3904 unique patients. These patients had 74,377 associated clinical documents, from which the NLP process indicated 2815 referenced HCQ retinopathy or retinopathy alone (including screening). From clinic codes 1299 individual patients (33.3% of the HCQ exposed population) were confirmed to have undergone screening; 1094 (84.2%) were female, mean age 54.8 years at the time of screening. Of those screened, NLP highlighted 568 references to HCQ retinopathy from 507 patients, within which 10 (0.77%) were confirmed to have HCQ retinopathy by manual validation. Conclusion The study has demonstrated that NLP is a promising technique to quickly identify subsets of patients (e.g. those taking HCQ) from large numbers of outpatient clinic letters. Further training of the algorithm may improve its ability to identify rare but important clinical outcomes. In a tertiary SLE centre, roughly one third of patients on HCQ were screened for HCQ retinopathy and 0.77% confirmed HCQ retinopathy. This is much lower than data from the previous studies in the US, but is in keeping with more recent publications in UK data, reflected in recent amendments to screening guidelines. Disclosure Y. Mushtaq: None. G. Tilston: None. K.L. Hyrich: None. A. Barton: None. N. Peek: None. B. Parker: None. D. Griffiths: None. J.H. Humphreys: None.

P008 Hydroxychloroquine-related adverse events, attrition and reasons for cessation over 5 years at a district general hospital: estimating future ophthalmology screening service use

Abstract Background/Aims Hydroxychloroquine (HCQ) is used widely in the management of rheumatic diseases and is considered to be generally well tolerated. HCQ ocular toxicity is a dose- and time-related reaction. The Royal College of Ophthalmologists (RCOphth) noted a low rate of drug discontinuation as a result of baseline testing (&amp;lt; 4%) and that prevalence data for HCQ ocular toxicity was based on treatment duration &amp;gt;5 years. The RCOphth updated their ocular toxicity screening guideline in 2020. A major change was removal of requirement for baseline screening, with screening commenced at 5 years of treatment unless risk factors are present. Though the number of patients starting HCQ treatment and the UK prescribing data could be estimated, the proportion of patients remaining on treatment for &amp;gt;5 years was stated to be unknown. We reviewed departmental HCQ prescribing, adverse event and attrition data over 5 years from Bolton NHS Foundation Trust, a district general hospital which serves a population of nearly 300,000. Methods Patients were identified as newly commencing HCQ if they had a shared care agreement in the calendar year 2016. Adverse events, attrition rates and reasons for cessation were obtained through review of hospital records over 5 years. Results In the 2016 calendar year, 100 patients commenced HCQ. The mean age was 58, and 70% patients were female. The most common indication was rheumatoid arthritis (75%). At 1 year, 30% of patients had stopped taking HCQ. At 5 years 57% of patients had stopped taking HCQ. The most common reason for cessation at 1 year was gastrointestinal symptoms (30%), and remained the most common reason at 5 years (19%). Eye symptoms were documented as reason for cessation in 7% of patients at 1 year, and 5% of patients at 5 years. On review of records, none of these were thought to be attributable to HCQ, though it was not recommenced. There were no patient deaths directly attributable to HCQ use. Conclusion A significant proportion of patients (57%) stopped taking HCQ after 5 years. The rate of attrition was highest within 12 months, which then almost doubled by 5 years. Centres wishing to estimate the workload related to HCQ retinopathy screening can capture their prescribing for patients newly starting HCQ and/or their catchment population numbers to estimate the Ophthalmology activity related to this 5 years' hence. This may help to fund and staff adequately to successfully carry out this drug safety activity. Disclosure D. Barahman: None. C. Saleh: None. A. Paul: None.