CHOROIDAL THINNING AND “STAIR-CASE” FOVEAL SIGN IN A PATIENT WITH ALPORT SYNDROME Nick Stanojcic, MBBS, Muhammad S. A. Raja, MRCOphth, Ben J. L. Burton, FRCOphth
Purpose: To quantitatively describe choroidal thickness in a patient with Alport syndrome and to qualitatively describe an unusual “stair-case” foveal sign. Methods: Retrospective case report. Results: This is the first case, to our knowledge, of the stair-case foveal sign. This is also the first case where choroidal thickness in a patient with Alport rsyndrome has been quantitatively described using enhanced depth imaging optical coherence tomography. Conclusion: Stair-case foveal sign and choroidal thinning are two new signs that clinicians can expect to encounter on optical coherence tomography imaging of patients with Alport syndrome. RETINAL CASES & BRIEF REPORTS 8:52–55, 2014
sign” and dot-and-fleck retinopathy. Interestingly, neither of these two signs was directly associated with the presence of macular thinning. Macular thinning is not pathognomonic of AS and has been reported in patients with proliferative sickle cell retinopathy and macular telangiectasia.6 Use of choroidal thickness measurements, especially with enhanced depth imaging OCT may help improve the understanding of many retinal and choroidal disorders.6–9 In this report, we set out to qualitatively describe a novel pattern of retinal thinning and quantitatively describe choroidal thickness in a patient with AS.
From the Department of Ophthalmology, the James Paget University Hospital NHS Foundation Trust, Norfolk, United Kingdom.
A
lport syndrome (AS) is a genetic, clinically heterogeneous disorder, characterized by progressive renal disease, often accompanied by sensorineural hearing loss and ocular changes.1 The prevalence has been estimated to be 1:5,000.2 Typical ocular features include perimacular “dotand-fleck” retinopathy, anterior lenticonus, posterior polymorphous corneal dystrophy, and cataract.2,3 More recently described features are macular retinoschisis,4 bull’s eye maculopathy and vitelliform macular detachment,5 and macular holes.2,6 Optical coherence tomography (OCT) is a relatively new tool used to assess retinal architecture in patients with AS. Although macular changes were previously not thought to be a common finding,2–4,6 a recent study found severe macular thinning in 70% of their cohort with preponderance to male sex (32 eyes with X-linked AS; spectral domain OCT).6 The two other common findings in this cohort were “the lozenge
Case Report A 43-year-old Caucasian male was diagnosed with AS aged 15 after persistent macroscopic hematuria, proteinuria, and sensorineural deafness. Renal biopsy in 1975 showed mild mesangial proliferation but negative immunofluorescence. The patient did not undergo any genetic testing. Since the clinical diagnosis, the patient received 3 renal transplants (1990, 2000, and 2005) for primary renal disease AS. His treatment comprised of oral antihypertensives, immunosuppressants, and anticoagulants. His systemic hypertension was well controlled. There was no family history of renal disease or deafness. He presented to our eye clinic with a 6-month history of a blurred patch in the left eye. Best-corrected Snellen visual acuity was 6/7.5 right (logMAR 0.1) and 6/20 left (logMAR 0.5). Anterior segment examination was unremarkable and there was no anterior lenticonus.
None of the authors have any financial/conflicting interests to disclose. Reprint requests: Nick Stanojcic, MBBS, James Paget University Hospital, Lowestoft Road, Gorleston, Great Yarmouth, Norfolk NR31 6LA, United Kingdom; e-mail: [email protected].
52
RETINA AND CHOROID IN ALPORT SYNDROME Fundoscopy revealed dull macular reflex (but no classic lozenge sign) and maculopathy bilaterally. The refraction was: R, −4.50/ −2.00 · 180; L, −4.50/−2.00 · 180. Fundus photographs and autofluorescence imaging (Figure 1) confirmed bilateral maculopathy. Spectral domain OCT included standard macular raster 6 mm · 6 mm and enhanced depth imaging for subfoveal choroidal thickness measurements (“Spectralis”; Heidelberg Engineering, Heidelberg, Germany). The most striking feature we encountered was an irregular pattern of foveal thinning (Figure 2). The typical clivus contour was lost and the foveal edge demonstrated a “staircase” pattern (Figure 2). The subfoveal choroidal thickness was markedly reduced, and this was quantitatively described (Table 1). Subfoveal choroidal thickness at the right foveal center was 59 mm and varied between 31 mm and 72 mm at the measured points in the right eye: at 500 mm, 1500 mm, and 2500 mm of the foveal center (Figure 2, left-hand side). The choroidal thickness at the left foveal center was 93 mm and varied between 45 mm and 100 mm at the measured points in the left eye: at 500 mm, 1500 mm, and 2500 mm of the foveal center (Figure 2, right-hand side). We measured choroidal thickness using the built-in caliper available with the spectral domain OCT machine (Spectralis). In addition, we noted peripapillary inner retinal schisis in both eyes (Figure 2, bottom row).
Discussion This is the first reported case, to our knowledge, of the stair-case foveal sign (Figure 2, top row, arrows) in a patient with AS. We propose that this may be a precursor of macular holes associated with AS. Although rarefaction of the inner choroid associated with AS has previously been mentioned in the literature,2 it has not been quantitatively described. The presence of anomalous collagen in the intercellular matrix of the retina and the choroid has been suggested as a possible cause for these findings.2
53
Severe macular thinning (on OCT) was found in 70% of eyes of patients with X-linked AS (32 eyes) in a recent study.6 Macular thinning, the lozenge sign, dot-and-fleck retinopathy, lenticonus, and the incidence of renal transplants were all more common in male patients.6 There has been a lot of interest in choroidal imaging with the use of enhanced depth imaging spectral domain OCT technique recently. Optical coherence tomography imaging studies reported that normal subfoveal choroidal thickness was 287 ± 76 mm (mean ± standard deviation) on the “Spectralis” (Heidelberg Engineering),7 and 272 ± 81 mm on the “Cirrus” (Carl Zeiss Meditec Inc, Dublin, CA) machines.8 Both these studies reported that the choroid was thickest subfoveally, thinned nasally more than temporally and that the choroidal thickness reduced with age. In our patient, the choroidal thickness was significantly lower than this, being between 3 and 5 times thinner subfoveally and varying between 49 mm and 100 mm within 2500 mm of the foveal centers. Our patient’s bilateral moderate myopia may have been a confounding factor. However, according to Nishida et al, even in very high myopes, subfoveal choroidal thickness was greater than in our patient. The mean subfoveal choroidal thickness for 35 highly myopic eyes of white patients (mean refractive error of −10.9 diopters [D], standard deviation ±3.6 D) and no other retinal pathology, was found to be 113.3 ± 53.9 mm (mean ± standard deviation).9 Choroidal thickness (measured by OCT) has been found to be decreased in patients may be influenced by systemic arterial
Fig. 1. Color fundus photographs and autofluorescence images (the right eye shown on the left-hand side). Color fundus photographs show dull macular reflex and maculopathy bilaterally (top row). Autofluorescence images show the disturbance of normal pattern of foveal autofluorescence (bottom row).
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RETINAL CASES & BRIEF REPORTS´ 2014 VOLUME 8 NUMBER 1
Fig. 2. Optical Coherence Tomography images of the patient’s maculae including enhanced depth imaging of the choroid on “Spectralis” (the right eye shown on the left-hand side). Top row: “stair-case” foveal sign with irregular foveal margin and clivus profile, more apparent in the left eye (vertical arrows). Middle row (horizontal B-scan): right eye—subfoveal choroidal thickness (59 mm) and choroidal thickness measured at 500 mm, 1500 mm, and 2500 mm from the foveal center, nasal-ward (69, 45, and 31 mm, respectively) and temporal-ward (72, 31, and 59 mm, respectively); left eye— subfoveal choroidal thickness (93 mm) and choroidal thickness measured at 500 mm, 1500 mm, and 2500 mm from the foveal center, nasal-ward (86, 62, and 45 mm, respectively) and temporal-ward (79, 80, and 100 mm, respectively); choroidal thickness measurement values are shown next to the corresponding vertical markers. Bottom row: inner retinal schisis with corresponding scanning laser ophthalmoscopy-like image showing the B-scan level.
hypertension and needs to be considered in anyone with chronic renal disease when the systemic hypertension is not adequately controlled. In the absence of other retinal diseases (e.g. macular telangiectasia, retinitis pigmentosa) and systemic diseases having the potential to affect macular (e.g. proliferative sickle cell retinopathy) or choroidal
thickness (e.g. uncontrolled systemic hypertension), our findings are probably largely the result of structural changes due to AS. Our findings contribute to the spectrum of previously reported retinal and choroidal OCT findings in patients with AS (macular holes,2 macular retinoschisis,4 bull’s eye maculopathy,5 and macular thinning6).
Table 1. Choroidal Thickness in Our Patient with AS as Measured with Spectralis Right Eye Temporal, mm 2500 59
1500 31
500 72
Left Eye
Subfoveal, mm 59
Nasal, mm 500 69
1500 45
2500 31
Nasal, mm 2500 45
1500 62
2500 86
Subfoveal, mm 93
Temporal, mm 500 79
1500 80
2500 100
The thickness was measured subfoveally and at 500 mm, 1500 mm, and 2500 mm away from the fovea both nasal-ward and temporalward, for each eye.
RETINA AND CHOROID IN ALPORT SYNDROME
In summary, this is the first case, to our knowledge, of the stair-case foveal sign and the first quantitative description of choroidal thinning associated with AS. Key words: Alport syndrome, enhanced depth imaging, macula, spectral domain optical coherence tomography. References 1. Hertz JM. Alport syndrome. Molecular genetic aspects. Dan Med Bull 2009;56:105–152. 2. Scassa C, Cupo G, Bruno M, et al. Early lamellar macular hole in Alport syndrome: case report and review of the literature. Eur Rev Med Pharmacol Sci 2012;16:122–125. 3. Colville DJ, Savige J. Alport syndrome. A review of the ocular manifestations. Ophthalmic Genet 1997;18:161–173.
55 4. Moisseiev E, Adiel B. Bilateral macular retinoschisis in a patient with X-linked Alport syndrome. Retin Cases Brief Rep 2012;6:4–6. 5. Fawzi AA, Lee NG, Eliott D, et al. Retinal findings in patients with Alport Syndrome: expanding the clinical spectrum. Br J Ophthalmol 2009;93:1606–1611. 6. Ahmed F, Kamae KK, Jones DJ, et al. Temporal macular thinning associated with x-linked Alport syndrome. JAMA Ophthalmol 2013;131:777–782. 7. Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol 2009;147:811–815. 8. Manjunath V, Taha M, Fujimoto JG, Duker JS. Choroidal thickness in normal eyes measured using Cirrus HD optical coherence tomography. Am J Ophthalmol 2010;150:325–329. 9. Nishida Y, Fujiwara T, Imamura Y, et al. Choroidal thickness and visual acuity in highly myopic eyes. Retina 2012;32:1229– 1236.
Purpose: To quantitatively describe choroidal thickness in a patient with Alport syndrome and to qualitatively describe an unusual “stair-case” foveal sign. Methods: Retrospective case report. Results: This is the first case, to our knowledge, of the stair-case foveal sign. This is also the first case where choroidal thickness in a patient with Alport rsyndrome has been quantitatively described using enhanced depth imaging optical coherence tomography. Conclusion: Stair-case foveal sign and choroidal thinning are two new signs that clinicians can expect to encounter on optical coherence tomography imaging of patients with Alport syndrome. RETINAL CASES & BRIEF REPORTS 8:52–55, 2014
sign” and dot-and-fleck retinopathy. Interestingly, neither of these two signs was directly associated with the presence of macular thinning. Macular thinning is not pathognomonic of AS and has been reported in patients with proliferative sickle cell retinopathy and macular telangiectasia.6 Use of choroidal thickness measurements, especially with enhanced depth imaging OCT may help improve the understanding of many retinal and choroidal disorders.6–9 In this report, we set out to qualitatively describe a novel pattern of retinal thinning and quantitatively describe choroidal thickness in a patient with AS.
From the Department of Ophthalmology, the James Paget University Hospital NHS Foundation Trust, Norfolk, United Kingdom.
A
lport syndrome (AS) is a genetic, clinically heterogeneous disorder, characterized by progressive renal disease, often accompanied by sensorineural hearing loss and ocular changes.1 The prevalence has been estimated to be 1:5,000.2 Typical ocular features include perimacular “dotand-fleck” retinopathy, anterior lenticonus, posterior polymorphous corneal dystrophy, and cataract.2,3 More recently described features are macular retinoschisis,4 bull’s eye maculopathy and vitelliform macular detachment,5 and macular holes.2,6 Optical coherence tomography (OCT) is a relatively new tool used to assess retinal architecture in patients with AS. Although macular changes were previously not thought to be a common finding,2–4,6 a recent study found severe macular thinning in 70% of their cohort with preponderance to male sex (32 eyes with X-linked AS; spectral domain OCT).6 The two other common findings in this cohort were “the lozenge
Case Report A 43-year-old Caucasian male was diagnosed with AS aged 15 after persistent macroscopic hematuria, proteinuria, and sensorineural deafness. Renal biopsy in 1975 showed mild mesangial proliferation but negative immunofluorescence. The patient did not undergo any genetic testing. Since the clinical diagnosis, the patient received 3 renal transplants (1990, 2000, and 2005) for primary renal disease AS. His treatment comprised of oral antihypertensives, immunosuppressants, and anticoagulants. His systemic hypertension was well controlled. There was no family history of renal disease or deafness. He presented to our eye clinic with a 6-month history of a blurred patch in the left eye. Best-corrected Snellen visual acuity was 6/7.5 right (logMAR 0.1) and 6/20 left (logMAR 0.5). Anterior segment examination was unremarkable and there was no anterior lenticonus.
None of the authors have any financial/conflicting interests to disclose. Reprint requests: Nick Stanojcic, MBBS, James Paget University Hospital, Lowestoft Road, Gorleston, Great Yarmouth, Norfolk NR31 6LA, United Kingdom; e-mail: [email protected].
52
RETINA AND CHOROID IN ALPORT SYNDROME Fundoscopy revealed dull macular reflex (but no classic lozenge sign) and maculopathy bilaterally. The refraction was: R, −4.50/ −2.00 · 180; L, −4.50/−2.00 · 180. Fundus photographs and autofluorescence imaging (Figure 1) confirmed bilateral maculopathy. Spectral domain OCT included standard macular raster 6 mm · 6 mm and enhanced depth imaging for subfoveal choroidal thickness measurements (“Spectralis”; Heidelberg Engineering, Heidelberg, Germany). The most striking feature we encountered was an irregular pattern of foveal thinning (Figure 2). The typical clivus contour was lost and the foveal edge demonstrated a “staircase” pattern (Figure 2). The subfoveal choroidal thickness was markedly reduced, and this was quantitatively described (Table 1). Subfoveal choroidal thickness at the right foveal center was 59 mm and varied between 31 mm and 72 mm at the measured points in the right eye: at 500 mm, 1500 mm, and 2500 mm of the foveal center (Figure 2, left-hand side). The choroidal thickness at the left foveal center was 93 mm and varied between 45 mm and 100 mm at the measured points in the left eye: at 500 mm, 1500 mm, and 2500 mm of the foveal center (Figure 2, right-hand side). We measured choroidal thickness using the built-in caliper available with the spectral domain OCT machine (Spectralis). In addition, we noted peripapillary inner retinal schisis in both eyes (Figure 2, bottom row).
Discussion This is the first reported case, to our knowledge, of the stair-case foveal sign (Figure 2, top row, arrows) in a patient with AS. We propose that this may be a precursor of macular holes associated with AS. Although rarefaction of the inner choroid associated with AS has previously been mentioned in the literature,2 it has not been quantitatively described. The presence of anomalous collagen in the intercellular matrix of the retina and the choroid has been suggested as a possible cause for these findings.2
53
Severe macular thinning (on OCT) was found in 70% of eyes of patients with X-linked AS (32 eyes) in a recent study.6 Macular thinning, the lozenge sign, dot-and-fleck retinopathy, lenticonus, and the incidence of renal transplants were all more common in male patients.6 There has been a lot of interest in choroidal imaging with the use of enhanced depth imaging spectral domain OCT technique recently. Optical coherence tomography imaging studies reported that normal subfoveal choroidal thickness was 287 ± 76 mm (mean ± standard deviation) on the “Spectralis” (Heidelberg Engineering),7 and 272 ± 81 mm on the “Cirrus” (Carl Zeiss Meditec Inc, Dublin, CA) machines.8 Both these studies reported that the choroid was thickest subfoveally, thinned nasally more than temporally and that the choroidal thickness reduced with age. In our patient, the choroidal thickness was significantly lower than this, being between 3 and 5 times thinner subfoveally and varying between 49 mm and 100 mm within 2500 mm of the foveal centers. Our patient’s bilateral moderate myopia may have been a confounding factor. However, according to Nishida et al, even in very high myopes, subfoveal choroidal thickness was greater than in our patient. The mean subfoveal choroidal thickness for 35 highly myopic eyes of white patients (mean refractive error of −10.9 diopters [D], standard deviation ±3.6 D) and no other retinal pathology, was found to be 113.3 ± 53.9 mm (mean ± standard deviation).9 Choroidal thickness (measured by OCT) has been found to be decreased in patients may be influenced by systemic arterial
Fig. 1. Color fundus photographs and autofluorescence images (the right eye shown on the left-hand side). Color fundus photographs show dull macular reflex and maculopathy bilaterally (top row). Autofluorescence images show the disturbance of normal pattern of foveal autofluorescence (bottom row).
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RETINAL CASES & BRIEF REPORTS´ 2014 VOLUME 8 NUMBER 1
Fig. 2. Optical Coherence Tomography images of the patient’s maculae including enhanced depth imaging of the choroid on “Spectralis” (the right eye shown on the left-hand side). Top row: “stair-case” foveal sign with irregular foveal margin and clivus profile, more apparent in the left eye (vertical arrows). Middle row (horizontal B-scan): right eye—subfoveal choroidal thickness (59 mm) and choroidal thickness measured at 500 mm, 1500 mm, and 2500 mm from the foveal center, nasal-ward (69, 45, and 31 mm, respectively) and temporal-ward (72, 31, and 59 mm, respectively); left eye— subfoveal choroidal thickness (93 mm) and choroidal thickness measured at 500 mm, 1500 mm, and 2500 mm from the foveal center, nasal-ward (86, 62, and 45 mm, respectively) and temporal-ward (79, 80, and 100 mm, respectively); choroidal thickness measurement values are shown next to the corresponding vertical markers. Bottom row: inner retinal schisis with corresponding scanning laser ophthalmoscopy-like image showing the B-scan level.
hypertension and needs to be considered in anyone with chronic renal disease when the systemic hypertension is not adequately controlled. In the absence of other retinal diseases (e.g. macular telangiectasia, retinitis pigmentosa) and systemic diseases having the potential to affect macular (e.g. proliferative sickle cell retinopathy) or choroidal
thickness (e.g. uncontrolled systemic hypertension), our findings are probably largely the result of structural changes due to AS. Our findings contribute to the spectrum of previously reported retinal and choroidal OCT findings in patients with AS (macular holes,2 macular retinoschisis,4 bull’s eye maculopathy,5 and macular thinning6).
Table 1. Choroidal Thickness in Our Patient with AS as Measured with Spectralis Right Eye Temporal, mm 2500 59
1500 31
500 72
Left Eye
Subfoveal, mm 59
Nasal, mm 500 69
1500 45
2500 31
Nasal, mm 2500 45
1500 62
2500 86
Subfoveal, mm 93
Temporal, mm 500 79
1500 80
2500 100
The thickness was measured subfoveally and at 500 mm, 1500 mm, and 2500 mm away from the fovea both nasal-ward and temporalward, for each eye.
RETINA AND CHOROID IN ALPORT SYNDROME
In summary, this is the first case, to our knowledge, of the stair-case foveal sign and the first quantitative description of choroidal thinning associated with AS. Key words: Alport syndrome, enhanced depth imaging, macula, spectral domain optical coherence tomography. References 1. Hertz JM. Alport syndrome. Molecular genetic aspects. Dan Med Bull 2009;56:105–152. 2. Scassa C, Cupo G, Bruno M, et al. Early lamellar macular hole in Alport syndrome: case report and review of the literature. Eur Rev Med Pharmacol Sci 2012;16:122–125. 3. Colville DJ, Savige J. Alport syndrome. A review of the ocular manifestations. Ophthalmic Genet 1997;18:161–173.
55 4. Moisseiev E, Adiel B. Bilateral macular retinoschisis in a patient with X-linked Alport syndrome. Retin Cases Brief Rep 2012;6:4–6. 5. Fawzi AA, Lee NG, Eliott D, et al. Retinal findings in patients with Alport Syndrome: expanding the clinical spectrum. Br J Ophthalmol 2009;93:1606–1611. 6. Ahmed F, Kamae KK, Jones DJ, et al. Temporal macular thinning associated with x-linked Alport syndrome. JAMA Ophthalmol 2013;131:777–782. 7. Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol 2009;147:811–815. 8. Manjunath V, Taha M, Fujimoto JG, Duker JS. Choroidal thickness in normal eyes measured using Cirrus HD optical coherence tomography. Am J Ophthalmol 2010;150:325–329. 9. Nishida Y, Fujiwara T, Imamura Y, et al. Choroidal thickness and visual acuity in highly myopic eyes. Retina 2012;32:1229– 1236.
