Research
Brief Report
Paradoxical Changes of Retinal Nerve Fiber Layer Thickness in Uveitic Glaucoma Sanjay Asrani, MD; Daniel B. Moore, MD; Glenn J. Jaffe, MD
IMPORTANCE Measurement of retinal nerve fiber layer (RNFL) thickness using optical
coherence tomography can aid in the diagnosis and management of glaucoma. We observed a previously unreported phenomenon in eyes with uveitis-associated glaucoma in which paradoxical changes in RNFL thickness were noted. OBSERVATIONS Four eyes of 3 patients with uveitis-associated glaucoma had a relatively normal RNFL measurement on presentation during periods of active uveitis and raised intraocular pressure. Subsequent control of uveitis and intraocular pressure was associated with a paradoxical thinning of the RNFL and increased cupping. CONCLUSIONS AND RELEVANCE Normal-appearing measurements of RNFL thickness in patients with uveitis should be interpreted cautiously in those with a raised intraocular pressure. Physicians should recognize that continued thinning of the RNFL and increased cupping, despite good intraocular pressure control in such eyes, may be due to resolution of edema of the RNFL.
Corresponding Author: Sanjay Asrani, MD, Duke University Eye Center, PO Box 3802, Durham, NC 27710 ([email protected]).
JAMA Ophthalmol. 2014;132(7):877-880. doi:10.1001/jamaophthalmol.2014.954 Published online May 22, 2014.
O
ptical coherence tomography (OCT) is commonly used in glaucoma diagnosis and management. Thinning of the retinal nerve fiber layer (RNFL), measured using OCT, is indicative of glaucoma progression. Progressive glaucomatous change is also seen as increased cupping of the optic nerve. Three patients with uveitic glaucoma made us question this paradigm, and we urge physicians to use caution when relying on these modalities to evaluate such patients. This study was approved by the Duke University Institutional Review Board. A waiver of consent was obtained from all patients.
Report of Cases
Author Affiliations: Duke University Eye Center, Durham, North Carolina.
new superior arcuate changes. An Ahmed glaucoma tube was placed sequentially in both eyes. Two months postoperatively, he had an IOP of 12 mm Hg OU with 2 glaucoma eyedrops, no uveitis activity, but an increased CDR of 0.8 in both eyes. Optical coherence tomography documented further RNFL thinning both superotemporally and inferotemporally (Figure 1C). Increased frequency of IOP checks revealed a stable IOP in the low teens at all visits. Three months later, IOP and clinical examination were stable, but overall severe progressive RNFL OCT thinning was noted (Figure 1D). Subsequent visits for the next 2 years, however, were unchanged, with a stable visual field, IOP, and RNFL.
Case 2
Case 1 A 27-year-old man with bilateral uveitis secondary to Behcet disease was first evaluated in the glaucoma clinic 6 months after a fluocinolone acetonide–sustained drug delivery implant had been placed in both eyes. Visual acuity was 20/20 OU, intraocular pressure (IOP) was 22 mm Hg OU with 2 glaucoma eyedrops, and the slitlamp examination revealed quiet anterior chambers. He was bilaterally pseudophakic with symmetric cup-disc ratios (CDRs) of 0.5. Initial RNFL OCT was interpreted as normal in both eyes (Figure 1A). Six months later, IOP was 32 mm Hg OU, and the ophthalmic examination was otherwise unchanged. In both eyes, follow-up RNFL OCT demonstrated early inferotemporal thinning with mild superotemporal thickening (Figure 1B), and automated perimetry revealed
A 73-year-old man with a visual acuity of 20/20 OS and an IOP of 24 mm Hg with no eyedrops in the left eye had been diagnosed with idiopathic unilateral uveitis. Slitlamp examination revealed low-grade anterior uveitis in the left eye with a CDR of 0.7 and an inferior notch. Baseline RNFL OCT demonstrated corresponding inferotemporal thinning (Figure 2A). The inflammation resolved with a several-month slow taper of topical corticosteroids while the IOP was treated with topical medications. One year later, he had an IOP of 35 mm Hg OS with 3 glaucoma eyedrops, an active low-grade anterior uveitis, and early posterior synechiae formation. The CDR was unchanged, and RNFL OCT demonstrated slight thickening compared with the previous year (Figure 2B). The patient’s inflammation and IOP responded to topical corticosteroids, and he
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Research Brief Report
Changes of RNFL Thickness in Uveitic Glaucoma
Figure 1. Sequential RNFL OCT Scans in Bilateral Uveitis Baseline November 1, 2010 IR 20° ART • OCT ART (144) Q: 30 [MS]
Baseline November 1, 2010 IR 20° ART • OCT ART (T1) Q 32 [MS]
200 µm
200 µm
300 240 180 120 60 45
90 DUP
135
300
NS 110
200 µm
200 µm
0 0 TMP
TS 152
180 225 NAS Position [ ]
270 NP
315
360 TMP NS 124
240
TS 150
M 52
60 0 TMP
G 115
M 10
T 42
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
135
180 225 NAS Position [ ]
270 NP
315
PNFL Thickness, μm
PNFL Thickness, μm
60
200 µm
200 µm
0 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
Classification
60 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
TS 120
G 120
M 102
T M
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
PNFL Thickness, μm
PNFL Thickness, μm
60
200 µm
200 µm
0 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
NS 105
Classification
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
G 85
M 19
Outside normal limits
360 TMP
120 60 0 45
90 DUP
135
240
T 64 T1 90
M 73
180 225 NAS Position [ ]
270 NP
Classification
120 60
Outside normal limits
0 TMP
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
PNFL Thickness, μm
PNFL Thickness, μm
Follow-up 4 December 9, 2011 IR 20° • OCT ART (9) Q: 23 [M1]
300 240 180 120 60
200 µm
200 µm
0 0 TMP
45
90 DUP
240
135
180 225 NAS Position [ ]
270 NP
315
360 TMP TS 64
300 240 180 120 60 0 0 TMP
300 NS 78
240
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
180
180 120
Classification
60
G 73
M 74
T 54
Outside normal limits
0 0 TMP
180
Warning: Classification valid for white eyes only.
200 µm
M 77
315
240
0
360 TMP
300
T1 82
270 NP
180
60
200 µm
M 71
180 225 NAS Position [ ]
300
0 TMP
300
TS 99
Follow-up 4 December 9, 2011 IR 24° • OCT ART (14) Q: 34 [M1]
G 73
135
360 TMP
120
0 TMP
D
T 50
90 DUP
Classification
180
120
0 TMP
NS 92
45
August 26, 2011 Follow-up 2 IR 24° • OCT ART (25) Q: 22 [MS]
Warning: Classification valid for white eyes only.
TS 85
360 TMP
0
Within normal limits
240
240
M 100
315
60
60
300
0 T1 100
360 TMP
120
120
0 TMP
T1 150
M 113
300
M 52
315
180
240
180 G 31
360 TMP
240
0
360 TMP
200 µm
T 74
315
300
0 TMP
300 NS 145
Within normal limits
0 TMP
NS 100
270 NP
360 TMP
August 26, 2011 Follow-up 2 IR 24° • OCT ART (25) Q: 21 [M1]
TS 98
180 225 NAS Position [ ]
180
C
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
Classification
120 60
Outside normal limits
0 M 45
T1 61
0 TMP
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
A, Initial retinal nerve fiber layer (RNFL) scans 6 months after placement of a fluocinolone acetonide implant in both eyes. B, Follow-up scans 6 months later demonstrating early inferotemporal thinning and mild superotemporal thickening. C, Significant thinning 2 months later, following lowering of
intraocular pressure (IOP) after bilateral glaucoma surgery both superotemporally and inferotemporally. D, Follow-up scans 3 months later with overall severe progressive thinning despite apparent control of IOP.
achieved stability on a once-every-other-day corticosteroid regimen. At last follow-up 6 months later, he had an IOP of 11 mm Hg OS with 3 glaucoma eyedrops, with no uveitic activity detected. However, RNFL OCT demonstrated significant global thinning, despite a stable CDR, compared with the most recent scan as well as his baseline measurement (Figure 2C). Optical coherence tomography in the unaffected eye remained stable.
low-grade anterior uveitis (diagnosed as idiopathic on investigation) and a CDR of 0.7 with inferior thinning. She started to receive topical corticosteroids, and the following day, her IOP was 19 mm Hg OD. On OCT, the RNFL was thickened (Figure 3B). A month later, she had decreased inflammation with topical corticosteroids but an IOP of 35 mm Hg OD with 3 glaucoma eyedrops. On OCT, the RNFL had mild inferior thinning (Figure 3C). A trabeculectomy with mitomycin C was performed. Her postoperative course was uncomplicated, and at a follow-up 2 months later, she had an IOP of 18 mm Hg OD with a once-daily topical corticosteroid, no uveitic activity, and a CDR of 0.8 with an inferior notch. On OCT, there was progressive superotemporal and inferotemporal RNFL thinning (Figure 3D) with further severe global RNFL thinning 5 months later (Figure 3E). Optical coherence tomography in the unaffected eye remained stable.
Case 3 A 61-year-old woman with early open-angle glaucoma had a visual acuity of 20/20 OD and an IOP of 19 mm Hg OD with 1 glaucoma eyedrop. The CDR was 0.5, visual fields were full, and a baseline RNFL OCT was interpreted as normal (Figure 3A). A year later, the patient sought treatment for headaches. She had an IOP of 60 mm Hg OD. Slitlamp examination revealed 878
90 DUP
120
120
200 µm
135
Classification 45
180
0 M 132
90 DUP
May 6, 2011 Follow-up 1 IR 20° ART • OCT ART (34) Q: 30 [MS]
180
T1 181
45
Within normal limits
0 TMP
240
240
M 102
0
60
300
0 TMP
300
G 121
60
0 T1 177
M 115
360 TMP
200 µm
200 µm
T 91
120
120
May 6, 2011 Follow-up 1 IR 20° ART • OCT ART (17) Q: 27 [MS]
NS 112
180
240
Within normal limits
B
TS 158
240
180
Classification
120 0
M 123
T1 136
300
0 TMP
300
180 G 111
T 87
PNFL Thickness, μm
PNFL Thickness, μm
A
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Changes of RNFL Thickness in Uveitic Glaucoma
Brief Report Research
Figure 2. Sequential RNFL OCT Scans in Unilateral Anterior Uveitis Baseline December 6, 2010 IR 20° ART + OCT ART (100) Q: 24 [HS]
200 µm
200 µm
300 240 180 120
TS 101
60
200 µm
200 µm
0 0 TMP
300 NS 110
Follow-up 2 May 23, 2012 IR 20° ART + OCT ART (100) Q: 21 [HS]
C
45
90 DUP
240
135
180 225 NAS Position [ ]
270 NP
315
360 TMP NS 72
G 90
T 70
Classification
60 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
G 70
N 64
Outside normal limits
0 0 TMP
240 180 120 60 0 0 TMP
45
90 DUP
135
180 NAS
360 TMP
T 71
270 NP
315
360 TMP
Classification
120
Outside normal limits
60 0
T1 43
NI 91
225
Position [ ]
240 180
120
T1 65
NI 120
300
300
TS 84
180 N 92
PNFL Thickness, μm
PNFL Thickness, μm
A
0 TMP
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
Follow-up 1 November 23, 2011 IR 20° ART + OCT ART (100) Q: 13 [HS]
PNFL Thickness, μm
B
200 µm
200 µm
TS 113
240 180 120 60 0 0 TMP
300 NS 112
300
45
90 DUP
135
240 180
G 101
N 96
T 83
180 225 NAS Position [ ]
270 NP
315
360 TMP
Classification
120
Outside normal limits
60 0
NI 143
T1 74
0 TMP
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
A, Baseline retinal nerve fiber layer (RNFL) scan demonstrating inferotemporal thinning. B, Follow-up 1 year later during mild uveitis flare-up with slight RNFL thickening compared with previously. C, Subsequent scan 6 months later after
quiescence of uveitis with significant global thinning compared with previous scans.
Figure 3. Thickening Followed by Thinning of RNFL Measurements Associated With Flare-up and Control of Uveitis Baseline November 1, 2010 IR 20° ART • OCT ART (T1) Q 32 [MS]
200 µm
200 µm
300
300 240 180 120 60 45
90 DUP
135
300
NS 88
200 µm
200 µm
0 0 TMP
TS 150
Follow-up 4 January 6, 2012 IR 24° ART + OCT ART (16) Q: 23 [MS]
D
180 225 NAS Position [ ]
270 NP
315
TS 111
240 M 75
0 TMP
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
B
M 66
G 105 T1 124
270 NP
315
360 TMP
0 TMP
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
315
360 TMP
360 TMP
Follow-up 5 May 9, 2012 IR 24° ART + OCT ART (15) Q: 23 [MS]
E
300
120 60
200 µm
200 µm
0 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
TS 83
180 120 60 0 0 TMP
300
NS 47
240
240
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
180
Classification
120 60
G 51
T 51
M 43
Within normal limits
0 0 TMP
180 225 NAS Position [ ]
Classification
180
240
M 118
135
Outside normal limits
240
0 TMP
300
M 88
90 DUP
0
180 T 77
45
60
PNFL Thickness, μm
PNFL Thickness, μm
200 µm
NS 104
0
120
300
TS 147
60
240
M 78
T1 53
360 TMP
Follow-up 2 October 19, 2011 IR 20° ART + OCT ART (16) Q 28 [MS]
200 µm
120
300
NS 88 G 93
T 65
Within normal limits
0
M 106
180
180
Classification
120 60
T1 120
240
0 TMP
360 TMP
180 G 93
T 63
PNFL Thickness, μm
PNFL Thickness, μm
A
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
T1 40
360 TMP
M 54
Classification
120 60
Outside normal limits
0 0 TMP
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
Follow-up 3 November 11, 2011 IR 20° ART + OCT ART (16) Q: 27 [MS]
C
PNFL Thickness, μm
300
200 µm
200 µm
TS 153
180 120 60 0 0 TMP
300
NS 104
240
240
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
180 T 74
G 105 T1 103
M 64 M 112
Classification
120 60
Borderline
0 0 TMP
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
A, Baseline retinal nerve fiber layer (RNFL) scan interpreted as normal. B, Follow-up 1 year later during mild uveitis flare-up demonstrating overall thickening of the RNFL. C, Repeat scan 1 month following resolution of uveitic activity with mild inferior thinning of the RNFL. D, Scan 2 months after
trabeculectomy showing progressive RNFL thinning superotemporally and inferotemporally. E, Scan 5 months after trabeculectomy showing severe progressive RNFL thinning globally.
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Research Brief Report
Changes of RNFL Thickness in Uveitic Glaucoma
Discussion These cases highlight a previously unreported phenomenon in patients with uveitic glaucoma: “normal” RNFL measurements obtained during uncontrolled periods of uveitic activity with subsequent thinning following control of uveitis. These cases also demonstrate that despite apparent control of IOP and continued uveitis quiescence, the RNFL continued to thin and the optic nerve had increased cupping. When glaucoma is superimposed in an eye with uveitis, a normal-appearing RNFL thickness1-4 could lead a physician to be less aggressive in the management of IOP. Conversely, if a uveitis-associated normal-appearing RNFL becomes thinner due to uveitis control, it may appear as glaucoma progression. This finding may lead the physician to inappropriately conclude there has been an abrupt worsening of the glaucoma. When interpreting these measurements, physicians should recognize that normal values are for eyes without disease such as uveitis, thickness may vary with uveitic activity, and clinical judgment should be used to determine appropriate treatment.
ARTICLE INFORMATION
REFERENCES
Submitted for Publication: August 24, 2013; final revision received December 24, 2013; accepted December 29, 2013.
1. Wu H, de Boer JF, Chen TC. Reproducibility of retinal nerve fiber layer thickness measurements using spectral domain optical coherence tomography. J Glaucoma. 2011;20(8):470-476.
Published Online: May 22, 2014. doi:10.1001/jamaophthalmol.2014.954. Author Contributions: Drs Asrani and Moore had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Asrani, Jaffe. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Asrani, Moore. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Moore. Obtained funding: Jaffe. Study supervision: Asrani, Jaffe. Conflict of Interest Disclosures: None reported.
880
Furthermore, on ophthalmoscopic evaluation, the optic nerve head may erroneously appear normal. We hypothesize that this normal-appearing optic nerve is likely due to subclinical RNFL edema,5 and after appropriate uveitis control, the edema resolves, the cupping increases and the RNFL thickness decreases, occasionally to the dramatic degree demonstrated earlier. Two patients showed an increase in RNFL thickness with increased inflammation, indicating that some of the thickness was secondary to edema. Furthermore, increased thickness of the RNFL noted after cataract or glaucoma surgery6-8 could be due to mild uveitis that accompanies the postoperative course. Since none of the eyes demonstrated clinical edema, fluorescein angiograms were not obtained. It is possible that such testing may help determine if the normal-appearing nerve actually has some edema by revealing leakage. Although such a phenomenon could be due to resolution of RNFL edema, confirmation that a normal and stable IOP has been achieved is necessary in patients with uveitic glaucoma due to the labile nature of IOP control in such eyes.
2. Wu H, de Boer JF, Chen TC. Diagnostic capability of spectral-domain optical coherence tomography for glaucoma. Am J Ophthalmol. 2012;153(5): 815-826.e2. 3. Alasil T, Wang K, Keane PA, et al. Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography. J Glaucoma. 2013;22(7): 532-541. 4. Bendschneider D, Tornow RP, Horn FK, et al. Retinal nerve fiber layer thickness in normals measured by spectral domain OCT. J Glaucoma. 2010;19(7):475-482.
tomography characteristics of eyes with acute anterior uveitis. Isr Med Assoc J. 2012;14(9): 543-546. 6. Raghu N, Pandav SS, Kaushik S, Ichhpujani P, Gupta A. Effect of trabeculectomy on RNFL thickness and optic disc parameters using optical coherence tomography. Eye (Lond). 2012;26(8): 1131-1137. 7. Dada T, Behera G, Agarwal A, Kumar S, Sihota R, Panda A. Effect of cataract surgery on retinal nerve fiber layer thickness parameters using scanning laser polarimetry (GDxVCC). Indian J Ophthalmol. 2010;58(5):389-394. 8. El-Ashry M, Appaswamy S, Deokule S, Pagliarini S. The effect of phacoemulsification cataract surgery on the measurement of retinal nerve fiber layer thickness using optical coherence tomography. Curr Eye Res. 2006;31(5):409-413.
5. Shulman S, Goldenberg D, Habot-Wilner Z, Goldstein M, Neudorfer M. Optical coherence
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Brief Report
Paradoxical Changes of Retinal Nerve Fiber Layer Thickness in Uveitic Glaucoma Sanjay Asrani, MD; Daniel B. Moore, MD; Glenn J. Jaffe, MD
IMPORTANCE Measurement of retinal nerve fiber layer (RNFL) thickness using optical
coherence tomography can aid in the diagnosis and management of glaucoma. We observed a previously unreported phenomenon in eyes with uveitis-associated glaucoma in which paradoxical changes in RNFL thickness were noted. OBSERVATIONS Four eyes of 3 patients with uveitis-associated glaucoma had a relatively normal RNFL measurement on presentation during periods of active uveitis and raised intraocular pressure. Subsequent control of uveitis and intraocular pressure was associated with a paradoxical thinning of the RNFL and increased cupping. CONCLUSIONS AND RELEVANCE Normal-appearing measurements of RNFL thickness in patients with uveitis should be interpreted cautiously in those with a raised intraocular pressure. Physicians should recognize that continued thinning of the RNFL and increased cupping, despite good intraocular pressure control in such eyes, may be due to resolution of edema of the RNFL.
Corresponding Author: Sanjay Asrani, MD, Duke University Eye Center, PO Box 3802, Durham, NC 27710 ([email protected]).
JAMA Ophthalmol. 2014;132(7):877-880. doi:10.1001/jamaophthalmol.2014.954 Published online May 22, 2014.
O
ptical coherence tomography (OCT) is commonly used in glaucoma diagnosis and management. Thinning of the retinal nerve fiber layer (RNFL), measured using OCT, is indicative of glaucoma progression. Progressive glaucomatous change is also seen as increased cupping of the optic nerve. Three patients with uveitic glaucoma made us question this paradigm, and we urge physicians to use caution when relying on these modalities to evaluate such patients. This study was approved by the Duke University Institutional Review Board. A waiver of consent was obtained from all patients.
Report of Cases
Author Affiliations: Duke University Eye Center, Durham, North Carolina.
new superior arcuate changes. An Ahmed glaucoma tube was placed sequentially in both eyes. Two months postoperatively, he had an IOP of 12 mm Hg OU with 2 glaucoma eyedrops, no uveitis activity, but an increased CDR of 0.8 in both eyes. Optical coherence tomography documented further RNFL thinning both superotemporally and inferotemporally (Figure 1C). Increased frequency of IOP checks revealed a stable IOP in the low teens at all visits. Three months later, IOP and clinical examination were stable, but overall severe progressive RNFL OCT thinning was noted (Figure 1D). Subsequent visits for the next 2 years, however, were unchanged, with a stable visual field, IOP, and RNFL.
Case 2
Case 1 A 27-year-old man with bilateral uveitis secondary to Behcet disease was first evaluated in the glaucoma clinic 6 months after a fluocinolone acetonide–sustained drug delivery implant had been placed in both eyes. Visual acuity was 20/20 OU, intraocular pressure (IOP) was 22 mm Hg OU with 2 glaucoma eyedrops, and the slitlamp examination revealed quiet anterior chambers. He was bilaterally pseudophakic with symmetric cup-disc ratios (CDRs) of 0.5. Initial RNFL OCT was interpreted as normal in both eyes (Figure 1A). Six months later, IOP was 32 mm Hg OU, and the ophthalmic examination was otherwise unchanged. In both eyes, follow-up RNFL OCT demonstrated early inferotemporal thinning with mild superotemporal thickening (Figure 1B), and automated perimetry revealed
A 73-year-old man with a visual acuity of 20/20 OS and an IOP of 24 mm Hg with no eyedrops in the left eye had been diagnosed with idiopathic unilateral uveitis. Slitlamp examination revealed low-grade anterior uveitis in the left eye with a CDR of 0.7 and an inferior notch. Baseline RNFL OCT demonstrated corresponding inferotemporal thinning (Figure 2A). The inflammation resolved with a several-month slow taper of topical corticosteroids while the IOP was treated with topical medications. One year later, he had an IOP of 35 mm Hg OS with 3 glaucoma eyedrops, an active low-grade anterior uveitis, and early posterior synechiae formation. The CDR was unchanged, and RNFL OCT demonstrated slight thickening compared with the previous year (Figure 2B). The patient’s inflammation and IOP responded to topical corticosteroids, and he
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877
Research Brief Report
Changes of RNFL Thickness in Uveitic Glaucoma
Figure 1. Sequential RNFL OCT Scans in Bilateral Uveitis Baseline November 1, 2010 IR 20° ART • OCT ART (144) Q: 30 [MS]
Baseline November 1, 2010 IR 20° ART • OCT ART (T1) Q 32 [MS]
200 µm
200 µm
300 240 180 120 60 45
90 DUP
135
300
NS 110
200 µm
200 µm
0 0 TMP
TS 152
180 225 NAS Position [ ]
270 NP
315
360 TMP NS 124
240
TS 150
M 52
60 0 TMP
G 115
M 10
T 42
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
135
180 225 NAS Position [ ]
270 NP
315
PNFL Thickness, μm
PNFL Thickness, μm
60
200 µm
200 µm
0 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
Classification
60 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
TS 120
G 120
M 102
T M
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
PNFL Thickness, μm
PNFL Thickness, μm
60
200 µm
200 µm
0 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
NS 105
Classification
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
G 85
M 19
Outside normal limits
360 TMP
120 60 0 45
90 DUP
135
240
T 64 T1 90
M 73
180 225 NAS Position [ ]
270 NP
Classification
120 60
Outside normal limits
0 TMP
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
PNFL Thickness, μm
PNFL Thickness, μm
Follow-up 4 December 9, 2011 IR 20° • OCT ART (9) Q: 23 [M1]
300 240 180 120 60
200 µm
200 µm
0 0 TMP
45
90 DUP
240
135
180 225 NAS Position [ ]
270 NP
315
360 TMP TS 64
300 240 180 120 60 0 0 TMP
300 NS 78
240
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
180
180 120
Classification
60
G 73
M 74
T 54
Outside normal limits
0 0 TMP
180
Warning: Classification valid for white eyes only.
200 µm
M 77
315
240
0
360 TMP
300
T1 82
270 NP
180
60
200 µm
M 71
180 225 NAS Position [ ]
300
0 TMP
300
TS 99
Follow-up 4 December 9, 2011 IR 24° • OCT ART (14) Q: 34 [M1]
G 73
135
360 TMP
120
0 TMP
D
T 50
90 DUP
Classification
180
120
0 TMP
NS 92
45
August 26, 2011 Follow-up 2 IR 24° • OCT ART (25) Q: 22 [MS]
Warning: Classification valid for white eyes only.
TS 85
360 TMP
0
Within normal limits
240
240
M 100
315
60
60
300
0 T1 100
360 TMP
120
120
0 TMP
T1 150
M 113
300
M 52
315
180
240
180 G 31
360 TMP
240
0
360 TMP
200 µm
T 74
315
300
0 TMP
300 NS 145
Within normal limits
0 TMP
NS 100
270 NP
360 TMP
August 26, 2011 Follow-up 2 IR 24° • OCT ART (25) Q: 21 [M1]
TS 98
180 225 NAS Position [ ]
180
C
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
Classification
120 60
Outside normal limits
0 M 45
T1 61
0 TMP
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
A, Initial retinal nerve fiber layer (RNFL) scans 6 months after placement of a fluocinolone acetonide implant in both eyes. B, Follow-up scans 6 months later demonstrating early inferotemporal thinning and mild superotemporal thickening. C, Significant thinning 2 months later, following lowering of
intraocular pressure (IOP) after bilateral glaucoma surgery both superotemporally and inferotemporally. D, Follow-up scans 3 months later with overall severe progressive thinning despite apparent control of IOP.
achieved stability on a once-every-other-day corticosteroid regimen. At last follow-up 6 months later, he had an IOP of 11 mm Hg OS with 3 glaucoma eyedrops, with no uveitic activity detected. However, RNFL OCT demonstrated significant global thinning, despite a stable CDR, compared with the most recent scan as well as his baseline measurement (Figure 2C). Optical coherence tomography in the unaffected eye remained stable.
low-grade anterior uveitis (diagnosed as idiopathic on investigation) and a CDR of 0.7 with inferior thinning. She started to receive topical corticosteroids, and the following day, her IOP was 19 mm Hg OD. On OCT, the RNFL was thickened (Figure 3B). A month later, she had decreased inflammation with topical corticosteroids but an IOP of 35 mm Hg OD with 3 glaucoma eyedrops. On OCT, the RNFL had mild inferior thinning (Figure 3C). A trabeculectomy with mitomycin C was performed. Her postoperative course was uncomplicated, and at a follow-up 2 months later, she had an IOP of 18 mm Hg OD with a once-daily topical corticosteroid, no uveitic activity, and a CDR of 0.8 with an inferior notch. On OCT, there was progressive superotemporal and inferotemporal RNFL thinning (Figure 3D) with further severe global RNFL thinning 5 months later (Figure 3E). Optical coherence tomography in the unaffected eye remained stable.
Case 3 A 61-year-old woman with early open-angle glaucoma had a visual acuity of 20/20 OD and an IOP of 19 mm Hg OD with 1 glaucoma eyedrop. The CDR was 0.5, visual fields were full, and a baseline RNFL OCT was interpreted as normal (Figure 3A). A year later, the patient sought treatment for headaches. She had an IOP of 60 mm Hg OD. Slitlamp examination revealed 878
90 DUP
120
120
200 µm
135
Classification 45
180
0 M 132
90 DUP
May 6, 2011 Follow-up 1 IR 20° ART • OCT ART (34) Q: 30 [MS]
180
T1 181
45
Within normal limits
0 TMP
240
240
M 102
0
60
300
0 TMP
300
G 121
60
0 T1 177
M 115
360 TMP
200 µm
200 µm
T 91
120
120
May 6, 2011 Follow-up 1 IR 20° ART • OCT ART (17) Q: 27 [MS]
NS 112
180
240
Within normal limits
B
TS 158
240
180
Classification
120 0
M 123
T1 136
300
0 TMP
300
180 G 111
T 87
PNFL Thickness, μm
PNFL Thickness, μm
A
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Changes of RNFL Thickness in Uveitic Glaucoma
Brief Report Research
Figure 2. Sequential RNFL OCT Scans in Unilateral Anterior Uveitis Baseline December 6, 2010 IR 20° ART + OCT ART (100) Q: 24 [HS]
200 µm
200 µm
300 240 180 120
TS 101
60
200 µm
200 µm
0 0 TMP
300 NS 110
Follow-up 2 May 23, 2012 IR 20° ART + OCT ART (100) Q: 21 [HS]
C
45
90 DUP
240
135
180 225 NAS Position [ ]
270 NP
315
360 TMP NS 72
G 90
T 70
Classification
60 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
G 70
N 64
Outside normal limits
0 0 TMP
240 180 120 60 0 0 TMP
45
90 DUP
135
180 NAS
360 TMP
T 71
270 NP
315
360 TMP
Classification
120
Outside normal limits
60 0
T1 43
NI 91
225
Position [ ]
240 180
120
T1 65
NI 120
300
300
TS 84
180 N 92
PNFL Thickness, μm
PNFL Thickness, μm
A
0 TMP
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
Follow-up 1 November 23, 2011 IR 20° ART + OCT ART (100) Q: 13 [HS]
PNFL Thickness, μm
B
200 µm
200 µm
TS 113
240 180 120 60 0 0 TMP
300 NS 112
300
45
90 DUP
135
240 180
G 101
N 96
T 83
180 225 NAS Position [ ]
270 NP
315
360 TMP
Classification
120
Outside normal limits
60 0
NI 143
T1 74
0 TMP
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
A, Baseline retinal nerve fiber layer (RNFL) scan demonstrating inferotemporal thinning. B, Follow-up 1 year later during mild uveitis flare-up with slight RNFL thickening compared with previously. C, Subsequent scan 6 months later after
quiescence of uveitis with significant global thinning compared with previous scans.
Figure 3. Thickening Followed by Thinning of RNFL Measurements Associated With Flare-up and Control of Uveitis Baseline November 1, 2010 IR 20° ART • OCT ART (T1) Q 32 [MS]
200 µm
200 µm
300
300 240 180 120 60 45
90 DUP
135
300
NS 88
200 µm
200 µm
0 0 TMP
TS 150
Follow-up 4 January 6, 2012 IR 24° ART + OCT ART (16) Q: 23 [MS]
D
180 225 NAS Position [ ]
270 NP
315
TS 111
240 M 75
0 TMP
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
B
M 66
G 105 T1 124
270 NP
315
360 TMP
0 TMP
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
315
360 TMP
360 TMP
Follow-up 5 May 9, 2012 IR 24° ART + OCT ART (15) Q: 23 [MS]
E
300
120 60
200 µm
200 µm
0 45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
TS 83
180 120 60 0 0 TMP
300
NS 47
240
240
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
180
Classification
120 60
G 51
T 51
M 43
Within normal limits
0 0 TMP
180 225 NAS Position [ ]
Classification
180
240
M 118
135
Outside normal limits
240
0 TMP
300
M 88
90 DUP
0
180 T 77
45
60
PNFL Thickness, μm
PNFL Thickness, μm
200 µm
NS 104
0
120
300
TS 147
60
240
M 78
T1 53
360 TMP
Follow-up 2 October 19, 2011 IR 20° ART + OCT ART (16) Q 28 [MS]
200 µm
120
300
NS 88 G 93
T 65
Within normal limits
0
M 106
180
180
Classification
120 60
T1 120
240
0 TMP
360 TMP
180 G 93
T 63
PNFL Thickness, μm
PNFL Thickness, μm
A
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
T1 40
360 TMP
M 54
Classification
120 60
Outside normal limits
0 0 TMP
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
Follow-up 3 November 11, 2011 IR 20° ART + OCT ART (16) Q: 27 [MS]
C
PNFL Thickness, μm
300
200 µm
200 µm
TS 153
180 120 60 0 0 TMP
300
NS 104
240
240
45
90 DUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
180 T 74
G 105 T1 103
M 64 M 112
Classification
120 60
Borderline
0 0 TMP
45
90 SUP
135
180 225 NAS Position [ ]
270 NP
315
360 TMP
A, Baseline retinal nerve fiber layer (RNFL) scan interpreted as normal. B, Follow-up 1 year later during mild uveitis flare-up demonstrating overall thickening of the RNFL. C, Repeat scan 1 month following resolution of uveitic activity with mild inferior thinning of the RNFL. D, Scan 2 months after
trabeculectomy showing progressive RNFL thinning superotemporally and inferotemporally. E, Scan 5 months after trabeculectomy showing severe progressive RNFL thinning globally.
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879
Research Brief Report
Changes of RNFL Thickness in Uveitic Glaucoma
Discussion These cases highlight a previously unreported phenomenon in patients with uveitic glaucoma: “normal” RNFL measurements obtained during uncontrolled periods of uveitic activity with subsequent thinning following control of uveitis. These cases also demonstrate that despite apparent control of IOP and continued uveitis quiescence, the RNFL continued to thin and the optic nerve had increased cupping. When glaucoma is superimposed in an eye with uveitis, a normal-appearing RNFL thickness1-4 could lead a physician to be less aggressive in the management of IOP. Conversely, if a uveitis-associated normal-appearing RNFL becomes thinner due to uveitis control, it may appear as glaucoma progression. This finding may lead the physician to inappropriately conclude there has been an abrupt worsening of the glaucoma. When interpreting these measurements, physicians should recognize that normal values are for eyes without disease such as uveitis, thickness may vary with uveitic activity, and clinical judgment should be used to determine appropriate treatment.
ARTICLE INFORMATION
REFERENCES
Submitted for Publication: August 24, 2013; final revision received December 24, 2013; accepted December 29, 2013.
1. Wu H, de Boer JF, Chen TC. Reproducibility of retinal nerve fiber layer thickness measurements using spectral domain optical coherence tomography. J Glaucoma. 2011;20(8):470-476.
Published Online: May 22, 2014. doi:10.1001/jamaophthalmol.2014.954. Author Contributions: Drs Asrani and Moore had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Asrani, Jaffe. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Asrani, Moore. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Moore. Obtained funding: Jaffe. Study supervision: Asrani, Jaffe. Conflict of Interest Disclosures: None reported.
880
Furthermore, on ophthalmoscopic evaluation, the optic nerve head may erroneously appear normal. We hypothesize that this normal-appearing optic nerve is likely due to subclinical RNFL edema,5 and after appropriate uveitis control, the edema resolves, the cupping increases and the RNFL thickness decreases, occasionally to the dramatic degree demonstrated earlier. Two patients showed an increase in RNFL thickness with increased inflammation, indicating that some of the thickness was secondary to edema. Furthermore, increased thickness of the RNFL noted after cataract or glaucoma surgery6-8 could be due to mild uveitis that accompanies the postoperative course. Since none of the eyes demonstrated clinical edema, fluorescein angiograms were not obtained. It is possible that such testing may help determine if the normal-appearing nerve actually has some edema by revealing leakage. Although such a phenomenon could be due to resolution of RNFL edema, confirmation that a normal and stable IOP has been achieved is necessary in patients with uveitic glaucoma due to the labile nature of IOP control in such eyes.
2. Wu H, de Boer JF, Chen TC. Diagnostic capability of spectral-domain optical coherence tomography for glaucoma. Am J Ophthalmol. 2012;153(5): 815-826.e2. 3. Alasil T, Wang K, Keane PA, et al. Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography. J Glaucoma. 2013;22(7): 532-541. 4. Bendschneider D, Tornow RP, Horn FK, et al. Retinal nerve fiber layer thickness in normals measured by spectral domain OCT. J Glaucoma. 2010;19(7):475-482.
tomography characteristics of eyes with acute anterior uveitis. Isr Med Assoc J. 2012;14(9): 543-546. 6. Raghu N, Pandav SS, Kaushik S, Ichhpujani P, Gupta A. Effect of trabeculectomy on RNFL thickness and optic disc parameters using optical coherence tomography. Eye (Lond). 2012;26(8): 1131-1137. 7. Dada T, Behera G, Agarwal A, Kumar S, Sihota R, Panda A. Effect of cataract surgery on retinal nerve fiber layer thickness parameters using scanning laser polarimetry (GDxVCC). Indian J Ophthalmol. 2010;58(5):389-394. 8. El-Ashry M, Appaswamy S, Deokule S, Pagliarini S. The effect of phacoemulsification cataract surgery on the measurement of retinal nerve fiber layer thickness using optical coherence tomography. Curr Eye Res. 2006;31(5):409-413.
5. Shulman S, Goldenberg D, Habot-Wilner Z, Goldstein M, Neudorfer M. Optical coherence
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