A Case of Hydroxychloroquine Retinopathy with Screening Updates

Welcome back to Ready, Set, Retina! In the first episode of 2026, Daniel Epshtein, OD, FAAO, is joined by Sara LeMay, OD, FAAO to review a case of hydroxychloroquine (HCQ) retinopathy and key updates to screening guidelines.

Dr. LeMay is a medical optometrist at Retina Associates of Kentucky.

Overview of HCQ retinopathy screening

It has been 10 years since the American Academy of Ophthalmology (AAO) has provided some updates to their preferred practice patterns that are important for providing the most up-to-date screening for patients at risk of retinal toxicity taking hydroxychloroquine.

HCQ is at times critical in the successful treatment of diseases like systemic lupus erythematous (SLE), rheumatoid arthritis (RA), and other inflammatory and dermatological conditions, however it presents a risk of irreversible retinal toxicity.¹ While this medication has several practical uses in healthcare it is a silent threat to the health of the macula.

This update builds on prior guidelines given to us in 2011 and 2016 and provides expanded information on imaging and risk data. Due to a greater understanding of early structural changes that can be detected on imaging, as clinicians we can take action earlier to spare functional central vision.

Risk factors for retinal toxicity

Risk of toxicity continues to be highly dependent on dosage by weight and duration. If a patient is taking a daily dosage of ≤5mg/kg using their REAL weight then they have less than a 1% risk of developing retinal toxicity in the first 5 years of taking HCQ, and this risk is still less than 2% up to 10 years.¹ However, this risk increases considerably to 20% after 20 years of taking HCQ.

Apart from considering dosage and duration, additional risk factors include renal disease and concurrent tamoxifen use. These risk factors were previously recognized in the 2016 recommendations but initiation of hydroxychloroquine at an older age was an added to this update.²

Case report: Hydroxychloroquine retinopathy

A 71-year-old female presented to reestablish ocular care after 3 years of lost follow-up. The patient presented with no ocular complaints. However, she weighed only 45kg (BMI 16.6), placing her significantly above the recommended dosing threshold of 5mg/kg/day.

Past ocular Hx: None
Past Med Hx: Systemic lupus erythematosus
Medications: Hydroxychloroquine 200mg BID for 16 years
BCVA: 20/20 OU
Slit lamp: Unremarkable aside from trace nuclear sclerosis bilaterally.

Imaging

Figure 1: Fundus and fundus autofluorescence (FAF) imaging of the patient at baseline. No bull’s eye maculopathy or RPE defects and hyper- or hypoautofluorescent defects on fundus photography and FAF, respectively.

^{Figure 1: Courtesy of Sara LeMay, OD, FAAO.}
Figures 2 and 3: Optical coherence tomography (OCT) imaging and thickness maps demonstrating parafoveal thinning OU (OS > OD). A "bright line" sign and a sombrero (or flying saucer) sign and can be appreciated OS.

^{Figure 2: Courtesy of Sara LeMay, OD, FAAO.}

^{Figure 3: Courtesy of Sara LeMay, OD, FAAO.}

Figures 4 and 5: Comparison maps from an exam 4 years prior and during the current exam highlighting a loss of ~30 and ~40 microns OD and OS, respectively.

^{Figure 4: Courtesy of Sara LeMay, OD, FAAO.}

^{Figure 5: Courtesy of Sara LeMay, OD, FAAO.}

Figures 6 and 7: 10-2 visual field testing from the current exam (top) and from 4 years ago (bottom) showing that she had developed central defects OU over those 4 years.

^{Figure 6: Courtesy of Sara LeMay, OD, FAAO.}

^{Figure 7: Courtesy of Sara LeMay, OD, FAAO.}

Summary of findings

Parafoveal thinning on OCT (OS > OD)
Ellipsoid zone disruption
Central visual field defects
Significant overdosing relative to body weight

Diagnosis

The patient was determined to have hydroxychloroquine retinal toxicity. Risk factors for toxicity include cumulative dose, renal disease, concurrent tamoxifen use, and—newly added in 2026—initiation of hydroxychloroquine at an older age.

Co-management strategy

The prescribing rheumatologist was contacted and the decision was made to wean the patient off hydroxychloroquine gradually to avoid precipitating a lupus flare.

In cases such as this, collaboration with the prescribing provider is essential; hydroxychloroquine serves a critical systemic function, and discontinuation decisions must be made jointly to balance ocular and systemic risk.

Follow-up

When external limiting membrane loss becomes extensive, patients should continue to be monitored even after discontinuation, as progression can occur after cessation of the medication. Annual or biennial screening intervals remain practical and are preferred over the guideline-permitted 5-year interval for low-risk patients, given real-world challenges with patient recall and follow-up compliance.

For this patient, repeat OCT and visual fields obtained over the following year demonstrated stability; therefore, the patient was ultimately discharged from active monitoring.

3 key takeaways from the update

Disease pattern: Patients with European heritage tend to have a parafoveal disease pattern and patients of Eastern Asian heritage tend to have a paracentral disease pattern. However, it was emphasized that both patterns should be effectively ruled out no matter the heritage.³
Dosage for obese patients: The recommended daily dosage of ≤5.0mg/kg of REAL weight remains the same.¹ Following the 2016 dosage recommendations, there was expressed concern that obese patients were at a higher risk while using the real weight. Due to this, severely obese patients should not exceed 400mg/day.³
Screening tests and schedule: The authors of this update emphasized that objective testing is considered the primary screening modality. OCT in addition to FAF are the primary tests and automated visual fields (10-2, 24-2) and multifocal electroretinography (mfERG) are confirmatory tests.³
1. Screening schedule remains unchanged and in the case where a patient does not have any risk factors, the patient can return for annual screening 5 years following their normal baseline screening.

Emphasis on earlier structural detection in HCQ retinopathy

Studies have provided clinicians with an increased understanding of the disease progression to detect early and subtle structural abnormalities on the OCT. It is no longer considered acceptable to detect severe toxicity such as bull’s eye maculopathy in patients that are compliant with screening recommendations.³

An earlier detection of retinal toxicity during a screening allows managing clinicians (prescribing HCQ provider and eyecare provider) more time to choose steps to balance retinal toxicity and treated disease. Communication with the prescribing physician is a key step in management of retinal toxicity.

Structure before function: OCT is the MVP

There was a shift from a focus on a functional screening to a structural screening. This means that OCT is the primary test to lead clinicians to early detection of HCQ toxicity.⁴

The retina tends to remain mostly normal for several years and early in the disease the patient is often asymptomatic. During this phase, an attentive clinician will notice subtle parafoveal thinning when comparing sequential OCTs (Figure 1).

This subtle thinning can occur several years before significant toxicity and before FAF, VF, or mfERG defects are detectable.³ When toxicity is detected at an early stage it can be advantageous because a clinician can balance the medical need to continuing the HCQ therapy versus cessation for risks of symptomatic vision loss.

Hydroxychloroquine damage predominantly occurs in the outer retina which includes the outer nuclear layer (ONL), ellipsoid zone (EZ) / retinal pigment epithelium (RPE) space which is referred to as the interdigitation zone (IZ) space, EZ, and external limiting membrane (ELM).¹ As these outer layers continue to degenerate this then leads to RPE disruption.

Figure 8: Anatomically normal OCT with highlighted outer retinal layers affected by HCQ.

^{Figure 8: Courtesy of Sara LeMay, OD, FAAO.}

The initial indicator of retinal damage can be seen as thinning in the parafoveal area typically seen in patients of European descent and/or paracentral thinning typically in those of East Asian descent.³ This can be best detected by using quantitative thickness values in Early Treatment Diabetic Retinopathy Study (ETDRS) measurement grids.

Figure 9: This b-scan OCT demonstrates subtle parafoveal thinning which is easiest to detect when evaluating the ETDRS grid.

^{Figure 9: Courtesy of Sara LeMay, OD, FAAO.}

Figure 10: ETDRS grid, the red zones in the inner ring indicate concentric parafoveal thinning suspicious for early or subclinical HCQ retinal toxicity.

^{Figure 10: Courtesy of Sara LeMay, OD, FAAO.}

Signs of intermediate and severe HCQ retinopathy

Anatomical changes that can begin to indicate intermediate damage are also subtle but critical to detect. At this stage, the damage is likely not to progress with cessation and even has shown evidence of reversal.

It is at this time that a clinician will begin to observe disappearance of the IZ line, which is the space in between the EZ and RPE, and degeneration of the EZ.¹ Due to these parafoveal changes a foveal “bright line” sign can be observed, which is the preservation of these structures in the fovea.

The combination of this thinning and structural deterioration, a sombrero or flying saucer sign can also be noticed.³ The deterioration of the ELM can be a critical anatomical change due to its relationship to indicate more advanced retinopathy. Discontinuing HCQ before the ELM is damaged can reduce the risk of progression.

Figure 11: This b-scan OCT demonstrates several changes seen in intermediate stages of retinal toxicity. The red arrow is showcasing an area of parafoveal EZ loss and ELM degradation. An early “bright line” can also be seen in this scan.

^{Figure 11: Courtesy of Sara LeMay, OD, FAAO.}

While these earlier changes are primarily detected in the parafoveal area due to wide-spread use of central OCT. Wider field OCT can detect pericentral damage which appears as loss of lines. These changes can be further confirmed by secondary tests such as FAF, VF, and/or mfERG.

Ideally, retinal damage would be detected before late or severe stage where there is RPE disruption and atrophy. The visual acuity is preserved unless the atrophy involves the foveal center.¹

Focal RPE atrophy can further develop into concentric atrophy, or bull’s eye maculopathy, which has historically been the hallmark sign of HCQ toxicity. However, with improved adherence to screening protocols by patients and routine utilization of OCT to detect earlier structural changes, then bull’s eye maculopathy should be avoided in the future.

For a refresher on analyzing OCT imaging written by Dr. Epshtein, check out Into the Woods: Interpreting OCT Imaging in Retinal Disease!

Confirmatory tests to follow suspected

Other confirmatory tests include FAF, visual fields, and mfERG. Of all these tests, wide-pattern FAF is considered the most useful objective test due to the potential to detect parafoveal and pericentral retinal damage.³ The first indicator is increased autofluorescence which is seen as brightness. In more severe toxicity the areas are dark due to RPE atrophy.³

Functional testing includes visual field testing which results can be variable depending on the reliability of the patient. For parafoveal function the 10-2 field pattern should be used and the 24-2 or 30-2 pattern is required for pericentral function.³ It is a possibility that either pattern of damage can occur no matter the heritage of the patient so a 24-2C can test for both in a single test.

Another functional test is the multifocal electroretinogram which is as sensitive as a visual field but more objective and therefore less variable. However, this testing is not as readily available in most clinics outside of academic centers and/or larger referral clinics.

Spot damage, what is the next step?

The new focus on identifying retinopathy at different stages of severity allows us as clinicians to predict the risk of progression and central vision loss. Foveal preservation is key.

When the RPE is damaged and bull’s eye maculopathy is visible, the disease will likely progress into the fovea. Nonetheless, when retinopathy is detected before the loss of the ELM and EZ loss there is generally very limited, if any, progression after one year of discontinuing the medication.⁵

When there is suspicion of early toxicity, communication with the prescribing medical physician is critical to balance the medical need of HCQ versus discontinuation. Since we are able to detect subclinical toxicity, there are some patients who might continue HCQ with strict observation of progression. This decision is a collaboration between the eyecare provider, the prescribing physician, and the patient.

What’s coming next?

The future holds much promise as we lean into advancements in technology aiding in early detection of retinal toxicity. High-resolution imaging of the retinal cells (adaptive optics imaging) will enable specialized equipment to detect early damage.

More readily available equipment like en-face OCT will allow a clinician to determine which layer is thinning or altered. Automating analysis of imaging modalities with artificial intelligence remains a hopeful advancement for early detection as well. The main goal is earlier detection for improved visual preservation.