Retina
Macular Retinal Ganglion Cell–Inner Plexiform Layer Thickness in Patients on Hydroxychloroquine Therapy Min Gyu Lee,1 Sang Jin Kim,1 Don-Il Ham,1 Se Woong Kang,1 Changwon Kee,1 Jaejoon Lee,2 Hoon-Suk Cha,2 and Eun-Mi Koh2 1
Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Division of Rheumatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2
Correspondence: Sang Jin Kim, Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea; [email protected]. Submitted: July 2, 2014 Accepted: November 10, 2014 Citation: Lee MG, Kim SJ, Ham D-I, et al. Macular retinal ganglion cell–inner plexiform layer thickness in patients on hydroxychloroquine therapy. Invest Ophthalmol Vis Sci. 2015;56:396–402. DOI:10.1167/ iovs.14-15138
PURPOSE. We evaluated macular ganglion cell-inner plexiform layer (GC-IPL) thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with chronic exposure to hydroxychloroquine (HCQ). METHODS. This study included 130 subjects, who were divided into three groups: Group 1A, 55 patients with HCQ use ‡5 years; Group 1B, 46 patients with HCQ use 1000 g), significant correlations were not observed. CONCLUSIONS. This study revealed that macular GC-IPL thickness did not show definite correlations with HCQ use. However, some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL. Keywords: hydroxychloroquine, retinal ganglion cell, hydroxychloroquine retinopathy
ydroxychloroquine (HCQ), a chloroquine analogue and originally an antimalarial drug, is used widely in the treatment of various rheumatologic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Retinal toxicity from HCQ is a well-known side effect and is characterized classically by bilateral bull’s eye maculopathy sparing the foveal center.1 Patients with bull’s eye maculopathy may suffer from irreversible, sometimes progressive, loss of visual acuity, central visual field, and color vision.1,2 After HCQ has largely replaced chloroquine due to its better tolerability, retinal toxicity from HCQ has a lower incidence, but still remains a major concern because of its potentially irreversible visual loss and the considerable number of patients on HCQ therapy. Indeed, patients with HCQ retinopathy usually do not show significant recovery, and there often is continuing functional loss even after discontinuation of the drug. Therefore, early detection is important to minimize loss of visual function. The overall incidence of retinal toxicity from HCQ is low.2,3 A recent study of 3995 patients who previously used HCQ revealed that the incidence of definite or probable retinal toxicity was 0.65%. However, the risk of toxicity was markedly increased after 5 to 7 years of use (or 1000 g of cumulative dose) and exceeds 1%.4 Moreover, recent advances in objective imaging modalities, including spectral-domain optical coher-
ence tomography (SD-OCT) and fundus autofluorescence (FAF) can detect subtle changes of macula, which may reveal more patients with HCQ retinopathy.5 Previous histopathological studies of human retinas with chloroquine retinopathy showed destruction of photoreceptors and neuroretina.6–8 Rosenthal et al.9 reported that chloroquine caused an initial dramatic effect on the retinal ganglion cells (RGCs), with subsequent degeneration of RGCs and photoreceptors in rhesus monkeys. Hallberg et al.10 showed that chloroquine leads to morphologic and biochemical signs of phospholipidosis in the neuroretina, but does not affect phospholipid metabolism of the RPE of mice. Whether HCQ also impairs the RGCs in patients is not clear. A recent study by Pasadhika et al.11 reported that selective thinning of perifoveal RGC and inner plexiform layers was found in patients with chronic exposure to HCQ in the absence of functional or structural clinical changes involving the photoreceptor or RPE layers. However, this study had a small sample size (n ¼ 8), and the correlation between dose of HCQ and perifoveal thinning was not investigated. To evaluate retinal structural changes related to RGCs, measurement of the macular ganglion cell–inner plexiform layer (GC-IPL) thickness can be used. Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA) can automatically segment and
Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783
396
H
IOVS j January 2015 j Vol. 56 j No. 1 j 397
GC-IPL Thickness in Patients Taking Hydroxychloroquine TABLE 1. Demographic and Clinical Characteristics of the Patients Group 1A Parameters
Number of subjects 55 Age, y, mean 6 SD 44.1 6 12.0 Female, n (%) 46 (83.6) Body weight, kg, mean 6 SD 56.5 6 7.5 22.3 6 2.5 BMI, kg/m2, mean 6 SD Duration of use, mo, mean 6 SD 97.1 6 25.9 (range) (62–174) Cumulative dose, g, mean 6 SD 778.6 6 318.7 Daily dose, mg, mean 6 SD 268.9 6 78.5 Daily dose per ideal body weight, mg/kg, mean 6 SD 5.2 6 1.8 Number of patients whose daily dose ‡400 mg, n (%) 6 (10.9) Number of patients whose daily dose ‡6.5 mg/kg ideal body weight, n (%) 14 (25.5) Diagnosis of patients,* n (%) Systemic lupus erythematosus Sj¨ ogren syndrome Rheumatoid arthritis Others
Group 1B
HCQ Use ‡ 5 y HCQ Use < 5 y
43 4 4 7
(78.2) (7.3) (7.3) (12.7)†
Group 2 Group 1
46 101 37.9 6 13.6 41.3 6 13.1 43 (93.5) 89 (88.1) 57.2 6 9.5 56.8 6 8.6 22.6 6 3.2 22.4 6 2.9 31.2 6 16.9 67.1 6 39.7 (2–58) (2–174) 294.1 6 173.4 557.9 6 356.6 320.8 6 85.9 292.5 6 85.6 6.3 6 1.8 5.7 6 1.9 18 (23.1) 24 (23.8) 23 (50.0) 37 (36.6) 35 8 6 1
(76.1) (17.4) (13.0) (2.2)‡
78 12 10 8
Normal Controls 29 43.8 6 10.8 20 (69.0) NA NA NA NA NA NA NA NA
(77.2) (11.9) (9.9) (7.9)
NA NA NA NA
29 (28.7) 9 (8.9)
NA NA
Systemic disease, n (%) Kidney dysfunction Liver dysfunction
21 (38.2) 9 (16.4)
8 (17.4) 0 (0.0)
BMI, body mass index; NA, not applicable. * Seven patients were diagnosed with more than one disease. † Five patients were diagnosed with antiphospholipid antibody syndrome, three patients with mixed connective tissue disease. One of them had both diseases. ‡ One patient was diagnosed with dermatomyositis and systemic lupus erythematosus.
measure macular GC-IPL thickness by ganglion cell analysis (GCA) algorithm. The macular GC-IPL thickness by GCA algorithm has been reported to have diagnostic values in glaucoma patients.12–15 In the present study, we investigated the association between HCQ use and macular GC-IPL thickness of 101 patients on HCQ therapy by Cirrus HD-OCT GCA algorithm to find whether there were structural changes related to RGCs by chronic exposure to HCQ.
PATIENTS
AND
METHODS
A retrospective review of medical records of 101 patients who had used HCQ for the treatment of rheumatologic disease, and were referred to ophthalmology department for screening of HCQ retinopathy between December 2012 and August 2013, was conducted. This study was approved by the Institutional Review Board of the Samsung Medical Center, and the work was done in accordance with the Declaration of Helsinki. Exclusion criteria were known optic nerve diseases; glaucoma; retinal diseases, including conditions that may affect outer retinal structures on SD-OCT; inflammatory eye diseases; and media opacity that interfere clear fundus or OCT examination. According to the revised American Academy of Ophthalmology (AAO) guidelines regarding HCQ screening, all patients underwent screening examinations, including dilated fundus examination, visual field testing in the form of static, automated threshold perimetry (10-2 Humphrey Field Analyzer, Model 750I; Humphrey Instruments, Inc., San Leandro, CA, USA), FAF, and SD-OCT (Spectralis HRAþOCT; Heidelberg Engineering, Heidelberg, Germany).5 The HCQ retinopathy was categorized as early, moderate, or severe according to the prior criteria.16,17 In addition, the Cirrus HD-OCT GCA algorithm was used to detect the macular GC-IPL, and to measure the thickness of the overall average and minimum GC-
IPL within a 6 3 62 mm elliptical annulus area centered on the fovea. The GCA algorithm was described previously in detail.15,18 Eyes with segmentation error, which was defined as disruption of the detected border and/or border wandering, were excluded from the study. The GCA also was performed for normal control subjects who had no ocular diseases, including retinal diseases, glaucoma, and optic neuropathies. Because duration of HCQ use exceeding five years is a known risk factor for HCQ retinopathy, the 130 subjects were divided into three groups: Group 1A, 55 patients with HCQ use ‡ 5 years; Group 1B, 46 patients with HCQ use < 5 years; and Group 2, 29 normal controls.4 In addition, other risk factors for HCQ retinopathy, including daily dose and kidney or liver dysfunction, also were documented.4,5 Only the right eye of each participant was included for analysis. Average and minimum GC-IPL thickness of Group 1A and 1B patients were compared to those of Group 2 subjects. Average and minimum GC-IPL thickness of Group 1A patients were compared to those of Group 1B patients. In addition, Pearson correlation analysis was conducted between GC-IPL thickness and duration or total dose of HCQ use. The analysis was repeated after excluding patients with HCQ retinopathy and patients with high cumulative doses (>1000 g). All statistical analyses of the data were done using PASW Statistics 18 (SPSS, Inc., Chicago, IL, USA) and the significance level was set at a P < 0.05.
RESULTS Table 1 shows the demographic and HCQ-related clinical characteristics of all 130 patients. The mean age of 101 patients in Group 1 was 41.3 years, and 89 patients (88.1%) were female. Mean duration of HCQ use in Group 1 was 67.1 months and mean total exposure of HCQ was 557.9 g. The mean daily dose was 292.5 g and 24 (23.8%) patients had taken mean 400
IOVS j January 2015 j Vol. 56 j No. 1 j 398
0.816
80.6 6 5.8 0.816 80.3 6 6.9
32.8 6 24.5 0.005 0.005 * The average GC-IPL thickness was compared to that of Group 1B (independent t-test). † The average GC-IPL thickness was compared to that of Group 2 (independent t-test).
0.113
75.0 6 15.9 0.041 0.031 73.4 6 17.7 0.010 0.007 76.5 6 14.2
Minimum, lm P value I* P value II†
0.113
0.049 0.027
78.3 6 7.8 0.207 0.176
0.607 0.607
83.7 6 4.3 83.1 6 4.7
1000 g), significant correlations were not observed. These findings suggest that although some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL, thinning of GC-IPL was not a general phenomenon in patients with exposure to HCQ.
GC-IPL Thickness in Patients Taking Hydroxychloroquine
IOVS j January 2015 j Vol. 56 j No. 1 j 399
FIGURE 1. Photographs show HCQ retinopathy in the right (A) and left (B) eyes of a 31-year-old female who was diagnosed with SLE and had used HCQ for 119 months. A cumulative dose of HCQ was 786 g and the daily dose per ideal body weight was 4.4 mg/kg. Her BCVA was 20/20 in both eyes. Color fundus photographs and FAF show a bull’s eye pattern maculopathy and SD-OCT demonstrates loss of parafoveal photoreceptor layer in both eyes. Humphrey 10-2 visual field testing shows paracentral scotoma in both eyes. (C) Ganglion cell analysis of Cirrus HD-OCT reveals markedly reduced average and minimum macular GC-IPL thickness in both eyes.
This study investigated the possible role of measuring GCIPL thickness as an objective ancillary testing to detect HCQ retinopathy earlier. Although thin GC-IPL was observed especially in patients with HCQ retinopathy or high cumulative TABLE 3. Correlation Analysis Between Macular GC-IPL Thickness and Duration or Total Dose of HCQ Use in Patients on HCQ Therapy Average GC-IPL Thickness, lm
Minimum GC-IPL Thickness, lm
P Pearson P Pearson Value* Coefficient Value* Coefficient Group 1, n ¼ 101 Duration of HCQ use 0.001 Cumulative HCQ dose
Macular Retinal Ganglion Cell–Inner Plexiform Layer Thickness in Patients on Hydroxychloroquine Therapy Min Gyu Lee,1 Sang Jin Kim,1 Don-Il Ham,1 Se Woong Kang,1 Changwon Kee,1 Jaejoon Lee,2 Hoon-Suk Cha,2 and Eun-Mi Koh2 1
Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Division of Rheumatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2
Correspondence: Sang Jin Kim, Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea; [email protected]. Submitted: July 2, 2014 Accepted: November 10, 2014 Citation: Lee MG, Kim SJ, Ham D-I, et al. Macular retinal ganglion cell–inner plexiform layer thickness in patients on hydroxychloroquine therapy. Invest Ophthalmol Vis Sci. 2015;56:396–402. DOI:10.1167/ iovs.14-15138
PURPOSE. We evaluated macular ganglion cell-inner plexiform layer (GC-IPL) thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with chronic exposure to hydroxychloroquine (HCQ). METHODS. This study included 130 subjects, who were divided into three groups: Group 1A, 55 patients with HCQ use ‡5 years; Group 1B, 46 patients with HCQ use 1000 g), significant correlations were not observed. CONCLUSIONS. This study revealed that macular GC-IPL thickness did not show definite correlations with HCQ use. However, some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL. Keywords: hydroxychloroquine, retinal ganglion cell, hydroxychloroquine retinopathy
ydroxychloroquine (HCQ), a chloroquine analogue and originally an antimalarial drug, is used widely in the treatment of various rheumatologic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Retinal toxicity from HCQ is a well-known side effect and is characterized classically by bilateral bull’s eye maculopathy sparing the foveal center.1 Patients with bull’s eye maculopathy may suffer from irreversible, sometimes progressive, loss of visual acuity, central visual field, and color vision.1,2 After HCQ has largely replaced chloroquine due to its better tolerability, retinal toxicity from HCQ has a lower incidence, but still remains a major concern because of its potentially irreversible visual loss and the considerable number of patients on HCQ therapy. Indeed, patients with HCQ retinopathy usually do not show significant recovery, and there often is continuing functional loss even after discontinuation of the drug. Therefore, early detection is important to minimize loss of visual function. The overall incidence of retinal toxicity from HCQ is low.2,3 A recent study of 3995 patients who previously used HCQ revealed that the incidence of definite or probable retinal toxicity was 0.65%. However, the risk of toxicity was markedly increased after 5 to 7 years of use (or 1000 g of cumulative dose) and exceeds 1%.4 Moreover, recent advances in objective imaging modalities, including spectral-domain optical coher-
ence tomography (SD-OCT) and fundus autofluorescence (FAF) can detect subtle changes of macula, which may reveal more patients with HCQ retinopathy.5 Previous histopathological studies of human retinas with chloroquine retinopathy showed destruction of photoreceptors and neuroretina.6–8 Rosenthal et al.9 reported that chloroquine caused an initial dramatic effect on the retinal ganglion cells (RGCs), with subsequent degeneration of RGCs and photoreceptors in rhesus monkeys. Hallberg et al.10 showed that chloroquine leads to morphologic and biochemical signs of phospholipidosis in the neuroretina, but does not affect phospholipid metabolism of the RPE of mice. Whether HCQ also impairs the RGCs in patients is not clear. A recent study by Pasadhika et al.11 reported that selective thinning of perifoveal RGC and inner plexiform layers was found in patients with chronic exposure to HCQ in the absence of functional or structural clinical changes involving the photoreceptor or RPE layers. However, this study had a small sample size (n ¼ 8), and the correlation between dose of HCQ and perifoveal thinning was not investigated. To evaluate retinal structural changes related to RGCs, measurement of the macular ganglion cell–inner plexiform layer (GC-IPL) thickness can be used. Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA) can automatically segment and
Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783
396
H
IOVS j January 2015 j Vol. 56 j No. 1 j 397
GC-IPL Thickness in Patients Taking Hydroxychloroquine TABLE 1. Demographic and Clinical Characteristics of the Patients Group 1A Parameters
Number of subjects 55 Age, y, mean 6 SD 44.1 6 12.0 Female, n (%) 46 (83.6) Body weight, kg, mean 6 SD 56.5 6 7.5 22.3 6 2.5 BMI, kg/m2, mean 6 SD Duration of use, mo, mean 6 SD 97.1 6 25.9 (range) (62–174) Cumulative dose, g, mean 6 SD 778.6 6 318.7 Daily dose, mg, mean 6 SD 268.9 6 78.5 Daily dose per ideal body weight, mg/kg, mean 6 SD 5.2 6 1.8 Number of patients whose daily dose ‡400 mg, n (%) 6 (10.9) Number of patients whose daily dose ‡6.5 mg/kg ideal body weight, n (%) 14 (25.5) Diagnosis of patients,* n (%) Systemic lupus erythematosus Sj¨ ogren syndrome Rheumatoid arthritis Others
Group 1B
HCQ Use ‡ 5 y HCQ Use < 5 y
43 4 4 7
(78.2) (7.3) (7.3) (12.7)†
Group 2 Group 1
46 101 37.9 6 13.6 41.3 6 13.1 43 (93.5) 89 (88.1) 57.2 6 9.5 56.8 6 8.6 22.6 6 3.2 22.4 6 2.9 31.2 6 16.9 67.1 6 39.7 (2–58) (2–174) 294.1 6 173.4 557.9 6 356.6 320.8 6 85.9 292.5 6 85.6 6.3 6 1.8 5.7 6 1.9 18 (23.1) 24 (23.8) 23 (50.0) 37 (36.6) 35 8 6 1
(76.1) (17.4) (13.0) (2.2)‡
78 12 10 8
Normal Controls 29 43.8 6 10.8 20 (69.0) NA NA NA NA NA NA NA NA
(77.2) (11.9) (9.9) (7.9)
NA NA NA NA
29 (28.7) 9 (8.9)
NA NA
Systemic disease, n (%) Kidney dysfunction Liver dysfunction
21 (38.2) 9 (16.4)
8 (17.4) 0 (0.0)
BMI, body mass index; NA, not applicable. * Seven patients were diagnosed with more than one disease. † Five patients were diagnosed with antiphospholipid antibody syndrome, three patients with mixed connective tissue disease. One of them had both diseases. ‡ One patient was diagnosed with dermatomyositis and systemic lupus erythematosus.
measure macular GC-IPL thickness by ganglion cell analysis (GCA) algorithm. The macular GC-IPL thickness by GCA algorithm has been reported to have diagnostic values in glaucoma patients.12–15 In the present study, we investigated the association between HCQ use and macular GC-IPL thickness of 101 patients on HCQ therapy by Cirrus HD-OCT GCA algorithm to find whether there were structural changes related to RGCs by chronic exposure to HCQ.
PATIENTS
AND
METHODS
A retrospective review of medical records of 101 patients who had used HCQ for the treatment of rheumatologic disease, and were referred to ophthalmology department for screening of HCQ retinopathy between December 2012 and August 2013, was conducted. This study was approved by the Institutional Review Board of the Samsung Medical Center, and the work was done in accordance with the Declaration of Helsinki. Exclusion criteria were known optic nerve diseases; glaucoma; retinal diseases, including conditions that may affect outer retinal structures on SD-OCT; inflammatory eye diseases; and media opacity that interfere clear fundus or OCT examination. According to the revised American Academy of Ophthalmology (AAO) guidelines regarding HCQ screening, all patients underwent screening examinations, including dilated fundus examination, visual field testing in the form of static, automated threshold perimetry (10-2 Humphrey Field Analyzer, Model 750I; Humphrey Instruments, Inc., San Leandro, CA, USA), FAF, and SD-OCT (Spectralis HRAþOCT; Heidelberg Engineering, Heidelberg, Germany).5 The HCQ retinopathy was categorized as early, moderate, or severe according to the prior criteria.16,17 In addition, the Cirrus HD-OCT GCA algorithm was used to detect the macular GC-IPL, and to measure the thickness of the overall average and minimum GC-
IPL within a 6 3 62 mm elliptical annulus area centered on the fovea. The GCA algorithm was described previously in detail.15,18 Eyes with segmentation error, which was defined as disruption of the detected border and/or border wandering, were excluded from the study. The GCA also was performed for normal control subjects who had no ocular diseases, including retinal diseases, glaucoma, and optic neuropathies. Because duration of HCQ use exceeding five years is a known risk factor for HCQ retinopathy, the 130 subjects were divided into three groups: Group 1A, 55 patients with HCQ use ‡ 5 years; Group 1B, 46 patients with HCQ use < 5 years; and Group 2, 29 normal controls.4 In addition, other risk factors for HCQ retinopathy, including daily dose and kidney or liver dysfunction, also were documented.4,5 Only the right eye of each participant was included for analysis. Average and minimum GC-IPL thickness of Group 1A and 1B patients were compared to those of Group 2 subjects. Average and minimum GC-IPL thickness of Group 1A patients were compared to those of Group 1B patients. In addition, Pearson correlation analysis was conducted between GC-IPL thickness and duration or total dose of HCQ use. The analysis was repeated after excluding patients with HCQ retinopathy and patients with high cumulative doses (>1000 g). All statistical analyses of the data were done using PASW Statistics 18 (SPSS, Inc., Chicago, IL, USA) and the significance level was set at a P < 0.05.
RESULTS Table 1 shows the demographic and HCQ-related clinical characteristics of all 130 patients. The mean age of 101 patients in Group 1 was 41.3 years, and 89 patients (88.1%) were female. Mean duration of HCQ use in Group 1 was 67.1 months and mean total exposure of HCQ was 557.9 g. The mean daily dose was 292.5 g and 24 (23.8%) patients had taken mean 400
IOVS j January 2015 j Vol. 56 j No. 1 j 398
0.816
80.6 6 5.8 0.816 80.3 6 6.9
32.8 6 24.5 0.005 0.005 * The average GC-IPL thickness was compared to that of Group 1B (independent t-test). † The average GC-IPL thickness was compared to that of Group 2 (independent t-test).
0.113
75.0 6 15.9 0.041 0.031 73.4 6 17.7 0.010 0.007 76.5 6 14.2
Minimum, lm P value I* P value II†
0.113
0.049 0.027
78.3 6 7.8 0.207 0.176
0.607 0.607
83.7 6 4.3 83.1 6 4.7
1000 g), significant correlations were not observed. These findings suggest that although some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL, thinning of GC-IPL was not a general phenomenon in patients with exposure to HCQ.
GC-IPL Thickness in Patients Taking Hydroxychloroquine
IOVS j January 2015 j Vol. 56 j No. 1 j 399
FIGURE 1. Photographs show HCQ retinopathy in the right (A) and left (B) eyes of a 31-year-old female who was diagnosed with SLE and had used HCQ for 119 months. A cumulative dose of HCQ was 786 g and the daily dose per ideal body weight was 4.4 mg/kg. Her BCVA was 20/20 in both eyes. Color fundus photographs and FAF show a bull’s eye pattern maculopathy and SD-OCT demonstrates loss of parafoveal photoreceptor layer in both eyes. Humphrey 10-2 visual field testing shows paracentral scotoma in both eyes. (C) Ganglion cell analysis of Cirrus HD-OCT reveals markedly reduced average and minimum macular GC-IPL thickness in both eyes.
This study investigated the possible role of measuring GCIPL thickness as an objective ancillary testing to detect HCQ retinopathy earlier. Although thin GC-IPL was observed especially in patients with HCQ retinopathy or high cumulative TABLE 3. Correlation Analysis Between Macular GC-IPL Thickness and Duration or Total Dose of HCQ Use in Patients on HCQ Therapy Average GC-IPL Thickness, lm
Minimum GC-IPL Thickness, lm
P Pearson P Pearson Value* Coefficient Value* Coefficient Group 1, n ¼ 101 Duration of HCQ use 0.001 Cumulative HCQ dose
