This presentation emphasizes the importance of screening for chloroquine retinopathy according to new AAO guidelines. While bull's eye maculopathy is a classic late-stage sign, initial photoreceptor damage typically occurs parafoveally in Europeans and peripherally near the arcades in Asians. Screening tests like automated visual fields and SD-OCT can detect toxicity before visible RPE damage, as irreversible progression often occurs by the time bull's eye maculopathy appears. Risk of toxicity depends on daily dose, with very thin patients at increased risk when dose is based on ideal rather than actual weight.

1. CHLOROQUINE RETINOPATHY

2. INTRODUCTION
• Chloroquine and hydroxychloroquine are the most
commonly antimalarials. They also used for the treatment
of many autoimmune and connective tissue diseases .
• Retinal toxicity from chloroquine (CQ) and its analogue
hydroxychloroquine (HCQ) has been recognized for many
years1
• Thus, it is important for ophthalmologists and other
physicians to understand the prevalence and risk factors for
retinopathy

3. PATHOPHYSIOLOGY1
• The mechanism of CQ and HCQ toxicity is not well
understood
• Binding to melanin in the RPE may serve to concentrate the
drugs and contribute to toxic effects.
• The primary damage is seen in photoreceptors and outer
nuclear layer and there is also disruption of the RPE.
• No anatomic features of the retina and RPE are known to
correlate with the parafoveal or extramacular patterns of
damage.

4. STATISTICAL RISK OF TOXICITY1
• Earlier literature shows that, the prevalence of CQ or HCQ
retinopathy seen only in few patients on long-term therapy and
only recognized in severe toxicity stage. (bull’s-eye changes).
• But now the prevalence of hydroxychloroquine retinopathy
ranges upto 7.5%.1,3
• However, some studies estimate that the percentage of toxic
maculopathy reaches up to 13.1%.5
• Daily dose was the most critical determinant of risk
• Particularly, Very thin patients are at increased risk when dose
is calculated by ideal weight

5. Advanced stage : Optic disc pallor and atrophy,
Attenuation of retinal arterioles,
fine granular pigmentary disturbances in the peripheral retina
prominent choroidal patterns.
Late stage : Development of an annular zone of depigmentation
of the retinal pigment epithelium surrounding the fovea
classically known as “bulls eye maculopathy”.
Early stage : Fine pigmentary stippling of the macula and loss
of the foveal light reflex
Normal
RETINAL MANIFESTATIONS OF CHLOROQUINE TOXICITY

6. DIAGNOSIS OF CHLOROQUINE RETINOPATHY
1. VISUAL FIELD ANALYSIS
Cluster of Paracentral
points with decreased
sensitivity
Partial bull’s eye
scotoma which may
resemble an arcuate
defect
Complete bull’s eye
scotoma which has a
complete ring defect
with relative sparing of
the fovea
10-2 for NON ASIAN PATIENTS , 30-2 for ASIAN PATIENTS

7. OPTICAL COHERENCE TOMOGRAPHY
• SD-OCT may detect changes in the
retinal architecture before the onset of
clinically apparent HCQ retinopathy.
• The typical feature is Flying saucer
sign. It is preservation of subfoveal IS-
OS junction with parafoveal IS-OS loss.
• The SD OCT shows localized thinning
of the photoreceptor layers in the
parafoveal region in non- Asian eyes or
near the arcades in Asian eyes. It is a
strong indicators of toxicity.

8. MULTIFOCAL ELECTRORETINOGRAPHY
• Multifocal Electroretinography may be the most sensitive test for early
HCQ retinopathy.
• It can localize deficiencies to the central macula, thereby detecting the
subtle changes characteristic of early HCQ retinopathy.
Multifocal ERG
Full field ERG

9. FUNDUS AUTOFLOURESCENCE
• Fundus autofluorescence
imaging can reveal early
parafoveal or extramacular
photoreceptor damage as an
area of increase
autofluorescence that may
precede thinning on SD OCT.

11. SCREENING FREQUENCY
Baseline Screening
• Fundus examination within first year of use
• Add visual fields and SD OCT if maculopathy is present
Annual Screening
• Begin after 5 yrs of use
• Sooner in the presence of major risk factors

12. MAJOR RISK FACTOR FOR TOXIC RETINOPATHY
2016 Guidelines
MINOR RISK FACTOR – AGE , LIVER DISEASE , GENETIC FACTOR

14. RECOMMENDED SCREENING
TESTS
Primary tests: ideally do both
• Automated visual fields
(appropriate to race)
• SD OCT
Other objective tests (as needed or
available) :
• mfERG
• FAF
Newer tests of possible value in
future:
• Microperimetry
• Adaptive optics retinal imaging
NOT RECOMMENDED
FOR SCREENING
•Fundus examination
•Time-domain OCT
•Fluorescein angiography
•Full-field ERG
•Amsler grid
•Color testing
•EOG

15. • This presentation is to emphasis the importance of screening and
newer AAO Guideliness regarding chloroquine retinopathy
• Although “Bulls eye maculopathy” is a classical feature , it is seen in
later stage. i.e. the time at which bulls eye maculopathy is seen, the
progression of disease is irreversible even after stoppage of drug.
• Similarly , initial photoreceptor damage in the classic parafoveal
distribution is common only in European population. But, most patients
of Asian population will show initial damage in a more peripheral
extramacular distribution i.e. near the vascular arcades
• Hence the screening tests are recommended which will detect
Chloroquine toxicity long before RPE damage is visible by imaging or
fundus examination.

16. REFERENCE
1. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF; American Academy of
Ophthalmology. Ophthalmology. 2016 Jun;123(6):1386-94. doi:
10.1016/j.ophtha.2016.01.058. Epub 2016
2. Marmor MF, Kellner U, Lai TY, et al. Revised recommendations
on screening for chloroquine and hydroxychloroquine
retinopathy. Ophthalmology 2011;118:415–22.
3. Melles RB, Marmor MF. JAMA Ophthalmol. 2014 Dec;132(12):1453-60. doi:
10.1001/jamaophthalmol.2014.3459. Erratum in: JAMA Ophthalmol. 2014
Dec;132(12):1493.
4. Michaelides M, Stover NB, Francis PJ, Weleber RG. Arch Ophthalmol. 2011
Jan;129(1):30-9. doi: 10.1001/archophthalmol.2010.321.
5. Palma Sánchez D, Rubio Velazquez E, Soro Marín S, Reyes García R. Retinal
toxicity due to antimalarials: frequency and risk factors. Reumatol Clin.

17. THANK YOU