Secondary Logo

Journal Logo

Original Study

Electroretinogram and Visual Field Correlation in Birdshot Chorioretinopathy

Ameri, Hossein MD, PhD; Naser, Maryam MD; Choudhury, Farzana MBBS, PhD; Rao, Narsing A. MD

Author Information
Asia-Pacific Journal of Ophthalmology: March-April 2021 - Volume 10 - Issue 2 - p 208-211
doi: 10.1097/APO.0000000000000374
  • Open

Abstract

Bridshot chorioretinopathy (BCR) is an inflammatory eye disease with characteristic hypopigmented fundus lesions.1 The disease is bilateral and typically associated with vitreous opacities, retinal vascular leakage, and cystoid macular edema. BCR is progressive, and if untreated, can result in significant vision loss. In addition to visual acuity, visual field (VF) is also affected1 and electroretinogram (ERG) is often abnormal.2,3 It is very rare, with an estimated population prevalence of 0.2 to 1.7 cases in 100,000.4 There is a strong association between histocompatibility leukocyte antigen-A29 and BCR.5,6

Because of recurrent and progressive nature of BCR, long-term treatment is required to prevent severe vision loss. Commonly, systemic corticosteroids are used as initial treatment or at exacerbation of the disease. However, steroid-sparing immunomodulatory therapy is the pillar of long-term treatment. Early and sustained treatment with proper regimen may even prevent typical BCR fundus lesions.7 Because corticosteroids and immunomodulatory therapy are both associated with potential serious side effects, proper regimen and dosing, titrated to the disease activity, are needed to minimize the risk of side effects while adequately suppressing the inflammation. ERG is commonly used to monitor the disease activity in BCR. Abnormalities of ERG have been shown to be associated with recurrence of inflammation,8 and treatment has been reported to result in ERG improvement in some patients.9 Interestingly, ERG improvement after treatment preceded clinical signs of recovery in some patients.10 Many studies have also reported VF changes along with ERG abnormalities in BCR.11,12 Since ERG measures global electrical activity of the retina, its correlation with Goldmann VF that measures visual function of the entire field of vision is plausible. The purpose of this study was to evaluate this hypothesis. Although serial Humphry VFs have been compared with ERG changes in BCR over time,13 to the best of our knowledge no study has compared the extent of VF loss with ERG parameters.

METHODS

This retrospective study included patients with BCR managed at a single center, USC Roski Eye Institute. Institutional review board approval was obtained from the Office for the Protection of Research Subjects at the University of Southern California before the start of the study. All patients had had ERG (Diagnosys LLC, Lowell, MA) and Goldmann Kinetic perimetry (Haag-Streit), often performed on the same date; if otherwise, the closest VF test to the ERG date was selected. ERGs were obtained using DTL electrodes, and were compliant with International Society for Clinical Electrophysiology of Vision standards. Both eyes of all patients were included except one whose VF was missing in the left eye. The V4e and I4e isopters of VF were assessed for possible association with both scotopic and photopic full field ERG parameters including the b-wave amplitude and implicit time of the dark adapted (DA) 0.01 ERG, and the b-wave and the a-wave amplitudes and implicit times of the DA 3.0, DA 10.0, and light adapted (LA) 3.0 ERG, and the amplitude and implicit time of the LA 30 Hz flicker ERG. The V4e isopter was selected because it is the largest isopter. Among other isopters, the I4e was the only one consistently present in all VF tests. For VF area measurements, Goldmann VF results were scanned to digital images. ImageJ software (National Institutes of Health, NIH, Bethesda, MD) was used to measure the size of each isopter, with blind spot and any scotomas excluded. All measurements were converted to square degrees based on the size of central 30°.

Statistical analyses were performed using SAS software 9.4 (SAS, Inc, Cary, NC). If available, observations from both eyes of the participants were used to test for correlation among the variables. To account for the within-subject correlation between the right and left eye measurements, the generalized estimating equation (GEE) was used for analysis. Analyses were performed using PROC GENMOD function in SAS. The output provides parameters estimates, standard errors of estimates, and P values. The V4e and I4e measurements were modeled as separate outcomes with each parameter of ERG as the main independent variable. Final models were adjusted for age and sex to control for any confounding by those. All tests for significance were at alpha level of 0.05.

RESULTS

Twenty-one eyes of 11 patients were included in this study. Patients’ age ranged from 50 to 73 years (mean 64 ± 9.4 years); 9 were female. Best-corrected visual acuity ranged from 20/20 to 20/60. Table 1 presents the results of GEE test for the V4e isopter. There were strong positive correlations between the size of V4e isopter and all scotopic a-wave and b-wave amplitudes: DA 0.01 b-wave (P < 0.0001), DA 3.0 a-wave (P < 0.0001), DA 3.0 b-wave (P < 0.0001), DA 10.0 a-wave (P < 0.0001), DA 10.0 b-wave (P < 0.0001). There were also strong positive correlations with all photopic amplitudes: LA 3.0 a-wave (P = 0.0019), LA 3.0 b-wave (P < 0.0001), and LA 30 Hz (P = 0.0026). On the contrary, the correlations between the V4e isopter and implicit times were less established; only DA 3.0 a-wave (P = 0.007) and LA 30 Hz (P < 0.0001) showed significant negative correlation; the remaining implicit times showed no correlation.

TABLE 1 - Correlation of the V4e Isopter of Goldmann Kinetic Perimetry and Electroretinogram Parameters
Estimate (β) SE P Value
Scotopic
 DA 0.01 b-wave Amplitude 198.28 27.35 <0.0001
Implicit time −197.89 193.62 0.31
 DA 3.0 a-wave Amplitude 283.57 51.79 <0.0001
Implicit time −2456.15 911.00 0.007
b-wave Amplitude 140.52 16.17 <0.0001
Implicit time 696.03 1186.94 0.56
 DA 10.0 a-wave Amplitude 247.58 42.24 <0.0001
Implicit time −3165.71 3691.14 0.39
b-wave Amplitude 175.14 23.81 <0.0001
Implicit time −593.10 335.19 0.08
Photopic
 LA 3.0 a-wave Amplitude 892.56 287.47 0.002
Implicit time 1937.39 1828.21 0.29
b-wave Amplitude 380.99 50.70 <0.0001
Implicit time −1125.65 1184.21 0.34
 LA 30Hz Amplitude 318.53 105.87 0.003
Implicit time −2972.06 652.13 <0.0001
DA indicates dark adapted; LA, light adapted; SE, standard error of estimate.

Table 2 shows the results of GEE test for the I4e isopter. In contrast to the V4e isopter, the I4e isopter did not show any correlations with any of the scotopic or photopic amplitudes. However, there were negative correlations between the size of I4e isopter and the scotopic DA 3.0 a-wave implicit time (P < 0.0001) and DA 10.0 b-wave implicit time (P = 0.0251), and photopic LA 3.0 b-wave implicit time (P < 0.0001). There were no correlations between the size of I4e isopter and other scotopic or photopic implicit times.

TABLE 2 - Correlation of the I4e Isopter of Goldmann Kinetic Perimetry and Electroretinogram Parameters
Estimate (β) SE P Value
Scotopic
 DA 0.01 b-wave Amplitude 7.09 4.92 0.15
Implicit time −43.43 23.64 0.07
 DA 3.0 a-wave Amplitude 10.69 7.57 0.16
Implicit time −443.90 83.16 <0.0001
b-wave Amplitude 4.88 3.33 0.14
Implicit time 4.54 61.33 0.94
 DA 10.0 a-wave Amplitude 3.44 4.11 0.40
Implicit time 317.36 466.78 0.50
b-wave Amplitude 3.70 2.96 0.21
Implicit time 40.62 35.82 0.03
Photopic
 LA 3.0 a-wave Amplitude 43.79 41.12 0.29
Implicit time −190.21 159.25 0.23
b-wave Amplitude 15.99 10.06 0.11
Implicit time −318.24 67.82 <0.0001
 LA 30 Hz Amplitude 12.49 8.79 0.16
Implicit time −186.99 138.73 0.18
DA indicates dark adapted; LA, light adapted; SE, standard error of estimate.

DISCUSSION

Full-field ERG is an objective test measuring global electroretinal function in response to light stimulus, and is generally unaffected by media opacity. Because it displays the actual electrical waveforms, it is relatively easy to detect gross changes, and since the unit numbers of amplitudes and implicit times are presented, any subtle change can be measured. These features of ERG make it a suitable test for monitoring the disease activity in BCR, in which ERG abnormalities have been well established. This study showing a strong correlation between the ERG and the largest isopter of kinetic perimetry highlights the role of ERG in BCR, and reveals that it could be predictive of visual function in this disease.

This study demonstrated a strong positive correlation of all standard ERG a-wave and b-wave amplitudes with the size of V4e isopter. In other words, decreased VF was associated with significant reduction in ERG amplitudes. However, there was no correlation between the majority of standard ERG a-wave and b-wave implicit times with the size of V4e isopter, except DA 3.0 a-wave and LA 30 Hz that showed a negative correlation, meaning that decreased VF was associated with increased implicit time in these parameters. Disproportionate involvement of the ERG amplitude compared to the implicit time in this study may suggest that retinal involvement in BCR may be segmental rather than diffuse retinal abnormality throughout the retina. This extrapolation is based on previous studies on retinal detachment which demonstrated decreased ERG amplitude without significant change in the implicit time,14 and proportional reduction of ERG amplitude with the extension of partial retinal detachment.15,16 Moreover, the study by Gordon et al,17 which demonstrated multiple foci of VF defect was the most common pattern in BCR, supports our hypothesis.

The ERG response is predominantly generated by photoreceptors and bipolar cells. Although inner retinal diseases affecting bipolar cells typically result in decreased b-wave amplitude, outer retinal diseases affecting photoreceptors result in decreased both a-wave and b-wave amplitudes. The changes in amplitude in this study were observed in both the a- and b-waves suggesting involvement of photoreceptors in BCR. Likewise, correlation of VF with the a-wave amplitude may link photoreceptor function with the VF in BCR.

As to why the I4e isopter did not display similar correlation with ERG as the V4e isopter, a possible explanation is that ERG measures electroretinal activity of the entire retina, and the V4e isopter is the largest isopter that assesses VF and therefore is the closest measurement to the entire retinal function. Our findings corroborate with those of Arya et al who reported worsening of ERG in only 3 of 10 BCR patients who showed progressive VF loss on standard 24-2 Humphrey VFs.13 Another possibility for more correlation of the V4e isopter with ERG could be more involvement of peripheral retina beyond the I4e isopter. Future large-scale studies on the pattern of VF defect in BCR may help to understand whether this holds true.

This study evaluated correlation of VF with ERG, which is an objective visual function test. Correlation of VF with structural changes of the retina has also been studied in BCR. There are conflicting reports on the correlation of fundus autofluorescence with VF. Although Jack et al18 did not find agreement between Goldmann VF and fundus autofluorescence, Boni et al19 reported macular or extramacular hypo autofluorescence to be related to Humphry VF mean deviation.

In our study, patients had relatively good visual acuity despite significant ERG and VF changes. Other studies have reported similar findings. Oh et al20 demonstrated worsening of both ERG and Goldmann VF in BCR over time, while visual acuity remained relatively stable. Islam et al showed improvement in both ERG and Humphry mean deviation after treatment of BCR, while visual acuity remained mostly stable.21 Tomkins-Netzer reported worsening of VF in patients who received short-term treatment while visual acuity remained stable.22 Although visual acuity can be severely affected secondary to cystoid macular edema and media opacity, it does not appear to correlate with the disease severity in BCR. Considering that visual acuity is a reflection of foveal function, and the foveal contribution to ERG and total VF is minimal, this disparity is not unexpected.

Retrospective nature and small sample size are main limitations of this study. In addition, this was a cross-sectional study with patients being at various stages of the disease severity. A longitudinal study on a large number of patients may allow assessment of correlations between the V4e isopter and ERG changes in individual patients over time. Another limitation of this study is that photopic negative response was not analyzed and therefore the exact functional status and involvement of the inner retina and its correlation with VF in BCR remain unknown.

In conclusion, this study showed a strong positive correlation between the size of the V4e isopter of Goldmann VF and all the amplitudes of standard ERG in BCR. This agreement between objective and subjective visual function tests underscores the role of full field ERG in monitoring the disease activity, and suggests that changes in the ERG amplitudes may reflect alterations in the entire field of vision in BCR.

REFERENCES

1. Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J Ophthalmol 1980; 89:31–45.
2. Gass JD. Vitiliginous chorioretinitis. Arch Ophthalmol 1981; 99:1778–1787.
3. Hirose T, Katsumi O, Pruett RC, Sakaue H, Mehta M. Retinal function in birdshot retinochoroidopathy. Acta Ophthalmol (Copenh) 1991; 69:327–337.
4. Minos E, et al. Birdshot chorioretinopathy: current knowledge and new concepts in pathophysiology, diagnosis, monitoring and treatment. Orphanet J Rare Dis 2016; 11:61.
5. Nussenblatt RB, Mittal KK, Ryan S, Green WR, Maumenee AE. Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune responsiveness to retinal S-antigen. Am J Ophthalmol 1982; 94:147–158.
6. Priem HA, et al. HLA typing in birdshot chorioretinopathy. Am J Ophthalmol 1988; 105:182–185.
7. Knecht PB, Papadia M, Herbort CP Jr. Early and sustained treatment modifies the phenotype of birdshot retinochoroiditis. Int Ophthalmol 2014; 34:563–574.
8. Zacks DN, Samson CM, Loewenstein J, Foster CS. Electroretinograms as an indicator of disease activity in birdshot retinochoroidopathy. Graefes Arch Clin Exp Ophthalmol 2002; 240:601–607.
9. Sobrin L, Lam BL, Liu M, Feuer WJ, Davis JL. Electroretinographic monitoring in birdshot chorioretinopathy. Am J Ophthalmol 2005; 140:52–64.
10. Holder GE, Robson AG, Pavesio C, Graham EM. Electrophysiological characterisation and monitoring in the management of birdshot chorioretinopathy. Br J Ophthalmol 2005; 89:709–718.
11. Priem HA, De Rouck A, De Laey JJ, Bird AC. Electrophysiologic studies in birdshot chorioretinopathy. Am J Ophthalmol 1988; 106:430–436.
12. Thorne JE, Jabs DA, Kedhar SR, Peters GB, Dunn JP. Loss of visual field among patients with birdshot chorioretinopathy. Am J Ophthalmol 2008; 145:23–28.
13. Arya B, Westcott M, Robson AG, Holder GE, Pavesio C. Pointwise linear regression analysis of serial Humphrey visual fields and a correlation with electroretinography in birdshot chorioretinopathy. Br J Ophthalmol 2015; 99:973–978.
14. Gong Y, Wu X, Sun X, Zhang X, Zhu P. Electroretinogram changes after scleral buckling surgery of retinal detachment. Doc Ophthalmol 2008; 117:103–109.
15. van Lith GH, van der Torren K, Vijfvinkel-Bruinenga S. ERG and VECPs in retinal detachments. Doc Ophthalmol 1981; 50:291–297.
16. Kim IT, Ha SM, Yoon KC. Electroretinographic studies in rhegmatogenous retinal detachment before and after reattachment surgery. Korean J Ophthalmol 2001; 15:118–127.
17. Gordon LK, et al. Longitudinal cohort study of patients with birdshot chorioretinopathy. IV. Visual field results at baseline. Am J Ophthalmol 2007; 144:829–837.
18. Jack LS, Agarwal A, Sepah YJ, Nguyen QD. Spatial agreement between Goldmann visual field defects and fundus autofluorescence in patients with birdshot chorioretinopathy. J Ophthalmic Inflamm Infect 2016; 6:18.
19. Boni C, Thorne JE, Spaide RF, et al. Fundus autofluorescence findings in eyes with birdshot chorioretinitis. Invest Ophthalmol Vis Sci 2017; 58:4015–4025.
20. Oh KT, Christmas NJ, Folk JC. Birdshot retinochoroiditis: long term follow-up of a chronically progressive disease. Am J Ophthalmol 2002; 133:622–629.
21. Islam F, et al. Safety profile and efficacy of tacrolimus in the treatment of birdshot retinochoroiditis: a retrospective case series review. Br J Ophthalmol 2018; 102:983–990.
22. Tomkins-Netzer O, Taylor SR, Lightman S. Long-term clinical and anatomic outcome of birdshot chorioretinopathy. JAMA Ophthalmol 2014; 132:57–62.
Keywords:

birdshot; electroretinogram; ERG; Goldmann visual field; uveitis

Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.