Ocular Immunology & Inflammation, 2014; 22(4): 263–269 ! Informa Healthcare USA, Inc. ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2013.844264
ORIGINAL ARTICLE
Ocular Coherence Tomographic and Clinical Characteristics in Patients of Punctuate Inner Choroidopathy Associated with Zonal Outer Retinopathy San-Ni Chen,
MD
and Jiunn-Feng Hwang,
MD
Department of Ophthalmology, Changhua Christian Hospital, Changhua City, Taiwan; and School of Medicine, Chungshan Medical University, Taichung, Taiwan
ABSTRACT Purpose: To describe the findings of optical coherence tomography and clinical characteristics in patients of zonal outer retinopathy associated with punctuate inner choroidopathy. Method: Review of consecutive cases on fundus photographs, spectral domain ocular coherence tomography, fluorescein angiography, indocyanine green angiography, visual field, and electrophysiological studies of patients with punctate inner choroidopathy and associated zonal outer retinopathy. Results: This study involves 4 patients suffering visual field defect far beyond the area corresponding to punctate inner choroidopathy lesions. Findings in optical coherence tomography include attenuated signals of photoreceptor inner/outer segment areas corresponding to visual field defect, and increased choroidal thickness. After treatment with immunosuppressive agents, improvements are noted in all 4 patients. Conclusion: Optical coherence tomography is helpful in the diagnosis of patients suffering zonal ocular outer retinopathy associated with punctate inner choroidopathy. All those patients responded well to immunosuppressive agents. Keywords: Immunosuppressive agents, optical coherence tomography, punctate inner choroidopathy, zonal outer retinopathy
METHOD
Punctate inner choroidopathy (PIC) is a disease manifested by multiple yellowish-white lesions in the inner choroid and outer retina, typically a disease of myopic females.1 Zonal outer retinal dysfunction beyond the area of choroidal lesions has been reported in cases of PIC and multifocal choroiditis (MFC).2–4 There have been some studies on optical coherence tomography (OCT)5–6 and indocyanine green angiographic findings4 in PIC, and other isolated cases of occult outer retinopathy associated with MFC.7 In this retrospective review of series cases, we describe the clinical, angiographic, electroretinographic (ERG), and serial OCT findings at the initial and convalescent phases before and after treatment in eyes of zonal occult outer retinopathy associated with PIC.
We retrospectively reviewed consecutive case records of patients of PIC associated with zonal outer retinopathy. The records include patients’ ocular history, slit-lamp biomicroscopoy, fundus photography, fluorescein angiography (FA) and indocyanine green angiography (ICG), Humphrey 30-2 visual field examination, spectral domain OCT (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA), and ERG. The average choroidal thickness in OCT is measured at the center of the fovea and 6 other loci, each 600 mm apart from one another and symmetrically away from the center. The study, with approval from the institutional review board of Changhua Christian Hospital
Received 23 February 2013; revised 3 August 2013; accepted 9 September 2013; published online 17 October 2013 Address correspondence to Dr. San-NI Chen, Department of Ophthalmology, Changhua Christian Hospital, Changhua City 500, Taiwan. E-mail: [email protected]
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264 S-N Chen and J-F Hwang TABLE 1. Demographic data of patients. Age/sex/eye 36/F/OS 25/F/OS 44/F/OD 34/F/OD
Initial /final VA 1.0/1.0 0.01/0.9 0.02/0.9 0.6/1.0
Refraction 11.5D 8.5D 16.0D 12.0D
Initial/final IS/OS signal
Initial/final CT (mm)
Attenuated/recovered Attenuated/recovered Attenuated/recovered Attenuated/recovered
143.7/118.1 206.4/125.1 113.8/92.1 154.2/114.5
VA, decimal visual acuity; IS/OS, inner segment/outer segment; CT, averaged choroidal thickness.
for the review of patient records, was carried out in adherence to the Helsinki Declaration. Demographic data of the patients are listed in Table 1.
CASE REPORTS
segment/outer segment in the left eye, except in area of punch-out lesions, where increased optical transmittance is observed. Choroidal thickness is much reduced as compared to the acute phase (125.1 mm, Figure 1B, lower). Visual field examination shows a subtotally recovered visual field with a paracentral scotoma left (Figure 1D, right).
Case 1 A 25-year-old myopic female patient (refraction OD: 7.75 D, OS: 8.5 D) had had acute onset of blurred vision without photopsia in the left eye for about 1 week. Previously, she had no complaint of any vision problem. At that time her best-corrected decimal visual acuity was 1.0 in the right eye and 0.01 in the left eye. No cells were found in the anterior chamber or in the vitreous of both eyes. Indirect funduscopy showed multiple pigmented lesions at posterior pole of her right eye, indicating previous attack of PIC. In her left eye, multiple cream-colored, punctuate lesions at posterior pole were noted (Figure 1A). OCT centered on the fovea demonstrated diffuse attenuated signal of photoreceptor inner segment/outer segment (IS/OS) junction with increased subfoveal choroidal thickness (206.4 mm) and some wavy, disintegrated RPE signals with overlying increased reflectivity, which spilled over into the outer nuclear layer corresponding to the cream-colored lesions in the left eye (Figure 1B, upper). For the right eye OCT showed multiple increased optical transmittances with overlying loss of outer nuclear layer corresponding to the pigment lesions. FA revealed profuse staining of the cream-colored lesion. ICG showed multiple dark, hypofluorescent spots corresponding to the PIC lesions surrounded by less darkened, coalescent hypofluorescent patches at posterior pole (Figure 1C). Visual field examination showed central scotoma contiguous with an enlarged blind spot and depressed light sensitivity in other areas in the left eye (Figure 1D, left). Enlarged blind spot and scotoma, corresponding to the pigment lesions, were noted in the right eye. Initially the patient was given prednisolone (25 mg bid) and mycophenolate sodium (360 mg bid) and the treatment was gradually tapered off within 3 months. Vision in her left eye improved in 6 weeks and reached 0.9, and 1.0 four months and 1 year later, respectively. The original cream-colored lesions shrunk and turned into punch-out lesions. OCT shows restoration of photoreceptor inner
Case 2 Another myopic female patient (refraction OD: 16.0 D, OS: 16.5 D), age 44, had had acute onset of visual loss in the right eye for 5 days. Her corrected decimal visual acuities were 0.02 and 0.8 in the right and left eyes, respectively, and both eyes showed no signs of cells or flare in the anterior chamber or in the vitreous. Funduscopic examination revealed several yellowish punch-out lesions in a linear fashion at the posterior pole of the right eye (Figure 2A). OCT showed a diffused disintegration of photoreceptor inner segment/outer segment junctions extending from fovea to the temporal punch-out lesion and beyond, with an averaged choroidal thickness of 113.8 mm (Figure 2B, upper). Increased optical transmittance corresponding to the punch-out lesions was also shown by OCT. FA demonstrated window defect and mild late staining in the punch-out lesion. ICG showed dark hypofluorescent lesions corresponding to the punch-out lesions with surrounding hypofluorescent patches at the posterior pole. Multifocal ERG showed a depressed area coinciding with the area of photoreceptor inner segment/outer segment junction abnormalities revealed in OCT. Visual field examination demonstrated central-nasal scotoma and an enlarged blind spot (Figure 2C, left). She was admitted for pulse steroid therapy with an administration of 250 mg methylprednisolone qid for 3 days, followed by prescriptions of prednisolone (20 mg qd) and mycophenolate sodium (360 mg bid). Oral prednisolone and mycophenolate were gradually tapered in 3 months. Her vision started to improve 2 weeks later and reached 0.8 at the 4-month follow-up. Recovery of photoreceptor inner segment/outer segment junction and reduced choroidal thickness are also noted in OCT (choroidal thickness: 92.0 mm, Figure 2B, lower) along with marked improvement of the visual field (Figure 2C, right). Ocular Immunology & Inflammation
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FIGURE 1. (A) Color fundus photography in case 1 shows multiple cream-colored lesions in the left eye. (B) Diffuse attenuated and disintegrated signals of photoreceptor inner segment/outer segment junctions in the macular area are noted in the left eye, along with wavy retinal pigment epithelial (RPE) lines and sub-RPE nodules corresponding to the cream-colored lesion in color fundus photography and marked increased choroidal thickness at the acute stage (upper). Three months later, the photoreceptor inner segment/outer segment junctions largely recovered. Smoothing of RPE and reduced choroidal thickening are also noted (lower). (C) Late phase fluorescein angiography in the left eye in case 1 at presentation shows profuse leakage of the cream-colored lesion. Indocyanine green angiography shows multiple dark, hypofluorescent spots corresponding to the PIC lesions surrounded by less darkened, coalescent hypofluorescent patches at posterior pole. (D) Visual field in the left eye at acute phase shows general depression and dark scotoma extending from central to temporal area (left). Four months later, the visual field is markedly improved except for a persistent paracentral scotoma, which corresponds to the choroidal scar formation nasal lower to fovea.
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FIGURE 2. (A) Funduscopic examination in case 2 reveals several yellowish punch-out lesions arranged in a linear fashion at the posterior pole in the right eye. (B) Optical coherence tomography (OCT) shows diffuse photoreceptor inner segment/outer segment disintegration extending from the fovea to the temporal punch-out lesion and beyond with an averaged choroidal thickness of 113.8 mm. Increased optical transmittance corresponding to the punch-out lesions is also shown by OCT (upper). Four months later, partial recovery of photoreceptor inner segment/outer segment is noted along with reduced choroidal thickness (92.1 mm, lower). (C) Visual field examination in case 2 at presentation demonstrates central-nasal scotoma and an enlarged blind spot (left). Marked improvement of the centro-nasal scotoma is noted 4 months later (right).
Case 3 A third female myopic patient, 34 years old, (refraction OD: 12.0 D, OS: 12.0 D) had had acute onset of blurred vision in the right eye for about 1 week. Her best-corrected decimal visual acuities were 0.6 in right eye and 1.0 in the left eye. A cluster of punctuate lesions temporal to the fovea were noted in the right
eye (Figure 3A). OCT showed diffused and attenuated signals of photoreceptor inner segment/outer segment junctions at the macular area. A localized RPE bump with increased overlying optical reflectivity from the temporal to the fovea was noted. Also obvious was an increased choroidal thickness in the right eye, averaging 154.2 mm, as compared to that in the left eye, 113.2 mm (Figure 3B, upper, middle). Ocular Immunology & Inflammation
PIC Associated with Outer Retinopathy
FIGURE 3. (A) Funduscopic photos in the right eye in case 3 showed a tessellated fundus with several small punctuate lesions temporal to the macula. (B) Optical coherence tomography shows diffuse attenuated signals of photoreceptor inner segment/outer segment junctions, a bumping RPE line temporal to the macular with overlying increased optical signals and increased choroidal thickness as compared to the left eye at acute phase (upper, middle). Two months later, the signals of photoreceptor inner segment/outer segment recovered a lot along with lessening choroidal thickening (lower).
Visual field showed an enlarged blind spot extending to the fovea. After prednisolone treatment for 8 weeks, her vision came back to 1.0, along with recovered photoreceptor inner segment/outer segment junctions and a decreased choroidal thickness (averaged thickness: 114.5 mm, Figure 3B, lower) as well as a recovered visual field.
Case 4 Another myopic female patient (refraction OD: 11.5 D, OS: 11.5 D), age 36 years, had complained of !
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paracentral scotoma in the left eye for 3 days. Her corrected decimal visual acuity for both eyes was 1.0. She had experienced an episode of blurred vision in the left eye for 1 year prior to this visit, which spontaneously resolved. No cells or flare could be observed in the anterior chamber or in the vitreous cavity. Funduscopic examination revealed a bilateral tessellated fundus with multiple faint yellowish linear and punch-out lesions in the left eye (Figure 4A). FA showed multiple hyperfluorescent spots and linear streaks in the early phase, but no obvious leakage in the later phase, and ICG demonstrated multiple hypofluorescent spots and linear, branching lesions, which were surrounded by a circular patch of lessdarkened hypofluorescence with polypoidal extension occupying the posterior pole (Figure 4B). OCT revealed diffused and attenuated signals of photoreceptor inner segment/outer segment junctions, from the nasal juxtafoveal area to the peripapillary area in the left eye. Increased thickness of subfoveal choroidal in the left eye, 143.7 mm, relative to the fellow eye, 103.8 mm, was also noticeable (Figure 4C, upper, middle). Visual field examination showed temporal scotoma contiguous to the enlarged blind spot (Figure 4D, left). Electrophysiologic tests showed decreased amplitude in multifocal ERG. The patient was given oral prednisolone (20 mg bid) and cyclosporine (100 mg bid), with noticeable restoration of photoreceptor inner segment/outer segment boundary and improvement of visual field 2 months later. An ICG performed at the 3–month follow-up shows resolution of the circular hypofluorescence patch with persistent hypofluorescent, linear, branch lesions. At the 12-month follow-up, OCT shows a subtotal recovery of IS/OS boundaries and resolution of choroidal thickening (Figure 4C, lower, choroidal thickness: 118.1 mm). Visual field examination also shows a completely recovered visual field (Figure 4D, right).
DISCUSSION Punctuate inner choroidopathy (PIC) and acute zonal occult outer retinopathy are both defined as AZOOR complex disorders. There have been several reports on patients developing zonal outer retinopathy, either in the same eye or in the fellow eye, after previous PIC attack.2–4 Gass proposed that these AZOOR complex disorders (PIC, AZOOR, etc.) probably represent spectrums of a single disease.8 Jampol and Becker propose that the "white dot syndromes" are different autoimmune diseases having common, but non-disease-specific genes interplaying with other genes and an environmental trigger.9 There have been reports indicating that persistent visual field defect,2–4 reduced amplitudes both in A and B waves in ERG, 2–3 and choroidal
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FIGURE 4. (A) Color fundus photography in case 4 shows a tessellated fundus with multiple yellowish spots and linear streak in the left eye. (B) Fluorescein angiography (left) at presentation shows hyperfluorescent spots and a linear streak without obvious leakage in late stage. Indocyanine green angiography demonstrates multiple hypofluorescent spots and linear, branching lesions, which are surrounded by a circular patch of less darkened hypofluorescence with polypoidal extension occupying the posterior pole in late phase. (C) Optical coherence tomography (OCT) in the left eye (middle) demonstrates diffuse attenuation of photoreceptor inner segment/outer segment boundaries from peripapillary area to nasal side of fovea along with increased choroidal thickness as compared to the right eye (upper). Partially recovered photoreceptor inner segment/outer segment boundaries are noted along with partial resolution of choroidal thickness 12 months later in the left eye (lower). (D) Humphrey 30-2 visual field test shows a large temporal scotoma contiguous with the blind spot and depressed central light sensitivity (left). Normalization of visual field is noted 12 months later (right).
hypofluorescent patches in late-phase ICG4 are clinical findings in cases of PIC-associated zonal outer retinopathy. Spaide et al. reported 2 cases of multifocal choroiditis and panuvieitis with enlarged blind spots and noted that photoreceptor inner segment/ outer segment junction loss in OCT at peripapillary area may be responsible for the persistent enlarged spots.7 In our study, spectral domain OCT reveals disintegration of photoreceptor inner segment/outer segment boundaries in all cases at the onset of symptoms. Increased choroidal thickness at the acute stage as compared to the thickness in the convalescent stage is a common feature in all 4 cases. Based on the findings of FA and ICG, it is obvious that outer retinopathy occurs along with
choroidal inflammation even when punctuate lesions are not active, as in cases 2 and 3. As choroidal abnormalities have never been reported at the acute stage in patients with pure AZOOR, we suspect that the outer retinopathy associated PIC is a different entity from pure AZOOR. In this review we have also noted that after immunosuppressive agents are administrated all cases have total or subtotal photoreceptor inner segment/outer segment boundaries restored, choroidal thickening resolved, and visual field recovered. In the case of pure AZOOR, the effect of immunosuppressive agents is still controversial.8 Here we show 4 consecutive cases of zonal outer retinopathy associated with PIC. Attenuation of Ocular Immunology & Inflammation
PIC Associated with Outer Retinopathy photoreceptor inner segment/outer segment boundaries, choroidal thickening at acute stage, and good response to immunosuppressive therapies with photoreceptor inner segment/outer segment boundaries recovered are noted in all 4 cases, but there are several limitations of this study. First is the small number of cases; second, the OCT machine used in our study does not have a tracking system, which makes minor disparities of scan position between each visit unavoidable, though we tried our best to scan on the same position. Since diurnal changes of choroidal thickness measured by OCT have been reported,11 those cases with small changes of choroidal thickness may represent variability in the time of day at which scans were acquired (though bigger diurnal changes are mainly noted in eyes with normal choroidal thickness, which is not the case in the patients in our series, who are all highly myopic and all have thin choroidal thickness). Manual segmentation used in our study is another issue that may make choroidal thickness measurement less reliable. More patients and better scanning by OCT are needed in the future to affirmatively characterize the clinical features of PIC.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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REFERENCES 1. Watzke RK, Packer AJ, Folk JC, et al. Punctate inner choroidopathy. Am J Ophthalmol. 1984;98:572–584. 2. Taira K, Nakazawa M, Takano Y, Ota T. Acute zonal occult outer retinopathy in the fellow eye 5 years after presentation of punctate inner choroidopathy. Graefes Arch Clin Exp Ophthalmol. 2006;244:880–882. 3. Holz FG, Kim RY, Schwartz SD, et al. Acute zonal occult outer retinopathy (AZOOR) associated with multifocal choroidopathy. Eye. 1994;8:77–83. 4. Saito A, Saito W, Furudate N, Ohno S. Indocyanine green angiography in a case of punctate inner choroidopathy associated with acute zonal occult outer retinopathy. Jpn J Ophthalmol. 2007;51:295–300. 5. Channa R, Ibrahim M, Sepah Y, et al. Characterization of macular lesions in punctate inner choroidopathy with spectral domain optical coherence tomography. J Ophthalmic Inflamm Infect. 2012;2:113–120. 6. Stepien KE, Carroll J. Using spectral-domain optical coherence tomography to follow outer retinal structure changes in a patient with recurrent punctate inner choroidopathy. J Ophthalmol. 2011;2011:753–741. 7. Spaide RF, Koizumi F, Freud KB. Photoreceptor outer segment abnormalities as a cause of blind spot enlargement in acute zonal occult outer retinopathy-complex diseases. Am J Ophthalmol. 2008;146:111–120. 8. Gass JDM. Are acute zonal occult outer retinopathy and the white spot syndromes (AZOOR complex) autoimmune disease? Am J Ophthalmol. 2003;135: 380–381. 9. Jampol LM, Becker G. White spot syndromes of the retina: a hypothesis based on the common genetic hypothesis of autoimmune/inflammatory disease. Am J Ophthalmol. 2003;135:376–379. 10. Tan CS, Ouyang Y, Ruiz H, Sadda SR. Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2012;53:261–266.
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ORIGINAL ARTICLE
Ocular Coherence Tomographic and Clinical Characteristics in Patients of Punctuate Inner Choroidopathy Associated with Zonal Outer Retinopathy San-Ni Chen,
MD
and Jiunn-Feng Hwang,
MD
Department of Ophthalmology, Changhua Christian Hospital, Changhua City, Taiwan; and School of Medicine, Chungshan Medical University, Taichung, Taiwan
ABSTRACT Purpose: To describe the findings of optical coherence tomography and clinical characteristics in patients of zonal outer retinopathy associated with punctuate inner choroidopathy. Method: Review of consecutive cases on fundus photographs, spectral domain ocular coherence tomography, fluorescein angiography, indocyanine green angiography, visual field, and electrophysiological studies of patients with punctate inner choroidopathy and associated zonal outer retinopathy. Results: This study involves 4 patients suffering visual field defect far beyond the area corresponding to punctate inner choroidopathy lesions. Findings in optical coherence tomography include attenuated signals of photoreceptor inner/outer segment areas corresponding to visual field defect, and increased choroidal thickness. After treatment with immunosuppressive agents, improvements are noted in all 4 patients. Conclusion: Optical coherence tomography is helpful in the diagnosis of patients suffering zonal ocular outer retinopathy associated with punctate inner choroidopathy. All those patients responded well to immunosuppressive agents. Keywords: Immunosuppressive agents, optical coherence tomography, punctate inner choroidopathy, zonal outer retinopathy
METHOD
Punctate inner choroidopathy (PIC) is a disease manifested by multiple yellowish-white lesions in the inner choroid and outer retina, typically a disease of myopic females.1 Zonal outer retinal dysfunction beyond the area of choroidal lesions has been reported in cases of PIC and multifocal choroiditis (MFC).2–4 There have been some studies on optical coherence tomography (OCT)5–6 and indocyanine green angiographic findings4 in PIC, and other isolated cases of occult outer retinopathy associated with MFC.7 In this retrospective review of series cases, we describe the clinical, angiographic, electroretinographic (ERG), and serial OCT findings at the initial and convalescent phases before and after treatment in eyes of zonal occult outer retinopathy associated with PIC.
We retrospectively reviewed consecutive case records of patients of PIC associated with zonal outer retinopathy. The records include patients’ ocular history, slit-lamp biomicroscopoy, fundus photography, fluorescein angiography (FA) and indocyanine green angiography (ICG), Humphrey 30-2 visual field examination, spectral domain OCT (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA), and ERG. The average choroidal thickness in OCT is measured at the center of the fovea and 6 other loci, each 600 mm apart from one another and symmetrically away from the center. The study, with approval from the institutional review board of Changhua Christian Hospital
Received 23 February 2013; revised 3 August 2013; accepted 9 September 2013; published online 17 October 2013 Address correspondence to Dr. San-NI Chen, Department of Ophthalmology, Changhua Christian Hospital, Changhua City 500, Taiwan. E-mail: [email protected]
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264 S-N Chen and J-F Hwang TABLE 1. Demographic data of patients. Age/sex/eye 36/F/OS 25/F/OS 44/F/OD 34/F/OD
Initial /final VA 1.0/1.0 0.01/0.9 0.02/0.9 0.6/1.0
Refraction 11.5D 8.5D 16.0D 12.0D
Initial/final IS/OS signal
Initial/final CT (mm)
Attenuated/recovered Attenuated/recovered Attenuated/recovered Attenuated/recovered
143.7/118.1 206.4/125.1 113.8/92.1 154.2/114.5
VA, decimal visual acuity; IS/OS, inner segment/outer segment; CT, averaged choroidal thickness.
for the review of patient records, was carried out in adherence to the Helsinki Declaration. Demographic data of the patients are listed in Table 1.
CASE REPORTS
segment/outer segment in the left eye, except in area of punch-out lesions, where increased optical transmittance is observed. Choroidal thickness is much reduced as compared to the acute phase (125.1 mm, Figure 1B, lower). Visual field examination shows a subtotally recovered visual field with a paracentral scotoma left (Figure 1D, right).
Case 1 A 25-year-old myopic female patient (refraction OD: 7.75 D, OS: 8.5 D) had had acute onset of blurred vision without photopsia in the left eye for about 1 week. Previously, she had no complaint of any vision problem. At that time her best-corrected decimal visual acuity was 1.0 in the right eye and 0.01 in the left eye. No cells were found in the anterior chamber or in the vitreous of both eyes. Indirect funduscopy showed multiple pigmented lesions at posterior pole of her right eye, indicating previous attack of PIC. In her left eye, multiple cream-colored, punctuate lesions at posterior pole were noted (Figure 1A). OCT centered on the fovea demonstrated diffuse attenuated signal of photoreceptor inner segment/outer segment (IS/OS) junction with increased subfoveal choroidal thickness (206.4 mm) and some wavy, disintegrated RPE signals with overlying increased reflectivity, which spilled over into the outer nuclear layer corresponding to the cream-colored lesions in the left eye (Figure 1B, upper). For the right eye OCT showed multiple increased optical transmittances with overlying loss of outer nuclear layer corresponding to the pigment lesions. FA revealed profuse staining of the cream-colored lesion. ICG showed multiple dark, hypofluorescent spots corresponding to the PIC lesions surrounded by less darkened, coalescent hypofluorescent patches at posterior pole (Figure 1C). Visual field examination showed central scotoma contiguous with an enlarged blind spot and depressed light sensitivity in other areas in the left eye (Figure 1D, left). Enlarged blind spot and scotoma, corresponding to the pigment lesions, were noted in the right eye. Initially the patient was given prednisolone (25 mg bid) and mycophenolate sodium (360 mg bid) and the treatment was gradually tapered off within 3 months. Vision in her left eye improved in 6 weeks and reached 0.9, and 1.0 four months and 1 year later, respectively. The original cream-colored lesions shrunk and turned into punch-out lesions. OCT shows restoration of photoreceptor inner
Case 2 Another myopic female patient (refraction OD: 16.0 D, OS: 16.5 D), age 44, had had acute onset of visual loss in the right eye for 5 days. Her corrected decimal visual acuities were 0.02 and 0.8 in the right and left eyes, respectively, and both eyes showed no signs of cells or flare in the anterior chamber or in the vitreous. Funduscopic examination revealed several yellowish punch-out lesions in a linear fashion at the posterior pole of the right eye (Figure 2A). OCT showed a diffused disintegration of photoreceptor inner segment/outer segment junctions extending from fovea to the temporal punch-out lesion and beyond, with an averaged choroidal thickness of 113.8 mm (Figure 2B, upper). Increased optical transmittance corresponding to the punch-out lesions was also shown by OCT. FA demonstrated window defect and mild late staining in the punch-out lesion. ICG showed dark hypofluorescent lesions corresponding to the punch-out lesions with surrounding hypofluorescent patches at the posterior pole. Multifocal ERG showed a depressed area coinciding with the area of photoreceptor inner segment/outer segment junction abnormalities revealed in OCT. Visual field examination demonstrated central-nasal scotoma and an enlarged blind spot (Figure 2C, left). She was admitted for pulse steroid therapy with an administration of 250 mg methylprednisolone qid for 3 days, followed by prescriptions of prednisolone (20 mg qd) and mycophenolate sodium (360 mg bid). Oral prednisolone and mycophenolate were gradually tapered in 3 months. Her vision started to improve 2 weeks later and reached 0.8 at the 4-month follow-up. Recovery of photoreceptor inner segment/outer segment junction and reduced choroidal thickness are also noted in OCT (choroidal thickness: 92.0 mm, Figure 2B, lower) along with marked improvement of the visual field (Figure 2C, right). Ocular Immunology & Inflammation
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FIGURE 1. (A) Color fundus photography in case 1 shows multiple cream-colored lesions in the left eye. (B) Diffuse attenuated and disintegrated signals of photoreceptor inner segment/outer segment junctions in the macular area are noted in the left eye, along with wavy retinal pigment epithelial (RPE) lines and sub-RPE nodules corresponding to the cream-colored lesion in color fundus photography and marked increased choroidal thickness at the acute stage (upper). Three months later, the photoreceptor inner segment/outer segment junctions largely recovered. Smoothing of RPE and reduced choroidal thickening are also noted (lower). (C) Late phase fluorescein angiography in the left eye in case 1 at presentation shows profuse leakage of the cream-colored lesion. Indocyanine green angiography shows multiple dark, hypofluorescent spots corresponding to the PIC lesions surrounded by less darkened, coalescent hypofluorescent patches at posterior pole. (D) Visual field in the left eye at acute phase shows general depression and dark scotoma extending from central to temporal area (left). Four months later, the visual field is markedly improved except for a persistent paracentral scotoma, which corresponds to the choroidal scar formation nasal lower to fovea.
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FIGURE 2. (A) Funduscopic examination in case 2 reveals several yellowish punch-out lesions arranged in a linear fashion at the posterior pole in the right eye. (B) Optical coherence tomography (OCT) shows diffuse photoreceptor inner segment/outer segment disintegration extending from the fovea to the temporal punch-out lesion and beyond with an averaged choroidal thickness of 113.8 mm. Increased optical transmittance corresponding to the punch-out lesions is also shown by OCT (upper). Four months later, partial recovery of photoreceptor inner segment/outer segment is noted along with reduced choroidal thickness (92.1 mm, lower). (C) Visual field examination in case 2 at presentation demonstrates central-nasal scotoma and an enlarged blind spot (left). Marked improvement of the centro-nasal scotoma is noted 4 months later (right).
Case 3 A third female myopic patient, 34 years old, (refraction OD: 12.0 D, OS: 12.0 D) had had acute onset of blurred vision in the right eye for about 1 week. Her best-corrected decimal visual acuities were 0.6 in right eye and 1.0 in the left eye. A cluster of punctuate lesions temporal to the fovea were noted in the right
eye (Figure 3A). OCT showed diffused and attenuated signals of photoreceptor inner segment/outer segment junctions at the macular area. A localized RPE bump with increased overlying optical reflectivity from the temporal to the fovea was noted. Also obvious was an increased choroidal thickness in the right eye, averaging 154.2 mm, as compared to that in the left eye, 113.2 mm (Figure 3B, upper, middle). Ocular Immunology & Inflammation
PIC Associated with Outer Retinopathy
FIGURE 3. (A) Funduscopic photos in the right eye in case 3 showed a tessellated fundus with several small punctuate lesions temporal to the macula. (B) Optical coherence tomography shows diffuse attenuated signals of photoreceptor inner segment/outer segment junctions, a bumping RPE line temporal to the macular with overlying increased optical signals and increased choroidal thickness as compared to the left eye at acute phase (upper, middle). Two months later, the signals of photoreceptor inner segment/outer segment recovered a lot along with lessening choroidal thickening (lower).
Visual field showed an enlarged blind spot extending to the fovea. After prednisolone treatment for 8 weeks, her vision came back to 1.0, along with recovered photoreceptor inner segment/outer segment junctions and a decreased choroidal thickness (averaged thickness: 114.5 mm, Figure 3B, lower) as well as a recovered visual field.
Case 4 Another myopic female patient (refraction OD: 11.5 D, OS: 11.5 D), age 36 years, had complained of !
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paracentral scotoma in the left eye for 3 days. Her corrected decimal visual acuity for both eyes was 1.0. She had experienced an episode of blurred vision in the left eye for 1 year prior to this visit, which spontaneously resolved. No cells or flare could be observed in the anterior chamber or in the vitreous cavity. Funduscopic examination revealed a bilateral tessellated fundus with multiple faint yellowish linear and punch-out lesions in the left eye (Figure 4A). FA showed multiple hyperfluorescent spots and linear streaks in the early phase, but no obvious leakage in the later phase, and ICG demonstrated multiple hypofluorescent spots and linear, branching lesions, which were surrounded by a circular patch of lessdarkened hypofluorescence with polypoidal extension occupying the posterior pole (Figure 4B). OCT revealed diffused and attenuated signals of photoreceptor inner segment/outer segment junctions, from the nasal juxtafoveal area to the peripapillary area in the left eye. Increased thickness of subfoveal choroidal in the left eye, 143.7 mm, relative to the fellow eye, 103.8 mm, was also noticeable (Figure 4C, upper, middle). Visual field examination showed temporal scotoma contiguous to the enlarged blind spot (Figure 4D, left). Electrophysiologic tests showed decreased amplitude in multifocal ERG. The patient was given oral prednisolone (20 mg bid) and cyclosporine (100 mg bid), with noticeable restoration of photoreceptor inner segment/outer segment boundary and improvement of visual field 2 months later. An ICG performed at the 3–month follow-up shows resolution of the circular hypofluorescence patch with persistent hypofluorescent, linear, branch lesions. At the 12-month follow-up, OCT shows a subtotal recovery of IS/OS boundaries and resolution of choroidal thickening (Figure 4C, lower, choroidal thickness: 118.1 mm). Visual field examination also shows a completely recovered visual field (Figure 4D, right).
DISCUSSION Punctuate inner choroidopathy (PIC) and acute zonal occult outer retinopathy are both defined as AZOOR complex disorders. There have been several reports on patients developing zonal outer retinopathy, either in the same eye or in the fellow eye, after previous PIC attack.2–4 Gass proposed that these AZOOR complex disorders (PIC, AZOOR, etc.) probably represent spectrums of a single disease.8 Jampol and Becker propose that the "white dot syndromes" are different autoimmune diseases having common, but non-disease-specific genes interplaying with other genes and an environmental trigger.9 There have been reports indicating that persistent visual field defect,2–4 reduced amplitudes both in A and B waves in ERG, 2–3 and choroidal
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FIGURE 4. (A) Color fundus photography in case 4 shows a tessellated fundus with multiple yellowish spots and linear streak in the left eye. (B) Fluorescein angiography (left) at presentation shows hyperfluorescent spots and a linear streak without obvious leakage in late stage. Indocyanine green angiography demonstrates multiple hypofluorescent spots and linear, branching lesions, which are surrounded by a circular patch of less darkened hypofluorescence with polypoidal extension occupying the posterior pole in late phase. (C) Optical coherence tomography (OCT) in the left eye (middle) demonstrates diffuse attenuation of photoreceptor inner segment/outer segment boundaries from peripapillary area to nasal side of fovea along with increased choroidal thickness as compared to the right eye (upper). Partially recovered photoreceptor inner segment/outer segment boundaries are noted along with partial resolution of choroidal thickness 12 months later in the left eye (lower). (D) Humphrey 30-2 visual field test shows a large temporal scotoma contiguous with the blind spot and depressed central light sensitivity (left). Normalization of visual field is noted 12 months later (right).
hypofluorescent patches in late-phase ICG4 are clinical findings in cases of PIC-associated zonal outer retinopathy. Spaide et al. reported 2 cases of multifocal choroiditis and panuvieitis with enlarged blind spots and noted that photoreceptor inner segment/ outer segment junction loss in OCT at peripapillary area may be responsible for the persistent enlarged spots.7 In our study, spectral domain OCT reveals disintegration of photoreceptor inner segment/outer segment boundaries in all cases at the onset of symptoms. Increased choroidal thickness at the acute stage as compared to the thickness in the convalescent stage is a common feature in all 4 cases. Based on the findings of FA and ICG, it is obvious that outer retinopathy occurs along with
choroidal inflammation even when punctuate lesions are not active, as in cases 2 and 3. As choroidal abnormalities have never been reported at the acute stage in patients with pure AZOOR, we suspect that the outer retinopathy associated PIC is a different entity from pure AZOOR. In this review we have also noted that after immunosuppressive agents are administrated all cases have total or subtotal photoreceptor inner segment/outer segment boundaries restored, choroidal thickening resolved, and visual field recovered. In the case of pure AZOOR, the effect of immunosuppressive agents is still controversial.8 Here we show 4 consecutive cases of zonal outer retinopathy associated with PIC. Attenuation of Ocular Immunology & Inflammation
PIC Associated with Outer Retinopathy photoreceptor inner segment/outer segment boundaries, choroidal thickening at acute stage, and good response to immunosuppressive therapies with photoreceptor inner segment/outer segment boundaries recovered are noted in all 4 cases, but there are several limitations of this study. First is the small number of cases; second, the OCT machine used in our study does not have a tracking system, which makes minor disparities of scan position between each visit unavoidable, though we tried our best to scan on the same position. Since diurnal changes of choroidal thickness measured by OCT have been reported,11 those cases with small changes of choroidal thickness may represent variability in the time of day at which scans were acquired (though bigger diurnal changes are mainly noted in eyes with normal choroidal thickness, which is not the case in the patients in our series, who are all highly myopic and all have thin choroidal thickness). Manual segmentation used in our study is another issue that may make choroidal thickness measurement less reliable. More patients and better scanning by OCT are needed in the future to affirmatively characterize the clinical features of PIC.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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REFERENCES 1. Watzke RK, Packer AJ, Folk JC, et al. Punctate inner choroidopathy. Am J Ophthalmol. 1984;98:572–584. 2. Taira K, Nakazawa M, Takano Y, Ota T. Acute zonal occult outer retinopathy in the fellow eye 5 years after presentation of punctate inner choroidopathy. Graefes Arch Clin Exp Ophthalmol. 2006;244:880–882. 3. Holz FG, Kim RY, Schwartz SD, et al. Acute zonal occult outer retinopathy (AZOOR) associated with multifocal choroidopathy. Eye. 1994;8:77–83. 4. Saito A, Saito W, Furudate N, Ohno S. Indocyanine green angiography in a case of punctate inner choroidopathy associated with acute zonal occult outer retinopathy. Jpn J Ophthalmol. 2007;51:295–300. 5. Channa R, Ibrahim M, Sepah Y, et al. Characterization of macular lesions in punctate inner choroidopathy with spectral domain optical coherence tomography. J Ophthalmic Inflamm Infect. 2012;2:113–120. 6. Stepien KE, Carroll J. Using spectral-domain optical coherence tomography to follow outer retinal structure changes in a patient with recurrent punctate inner choroidopathy. J Ophthalmol. 2011;2011:753–741. 7. Spaide RF, Koizumi F, Freud KB. Photoreceptor outer segment abnormalities as a cause of blind spot enlargement in acute zonal occult outer retinopathy-complex diseases. Am J Ophthalmol. 2008;146:111–120. 8. Gass JDM. Are acute zonal occult outer retinopathy and the white spot syndromes (AZOOR complex) autoimmune disease? Am J Ophthalmol. 2003;135: 380–381. 9. Jampol LM, Becker G. White spot syndromes of the retina: a hypothesis based on the common genetic hypothesis of autoimmune/inflammatory disease. Am J Ophthalmol. 2003;135:376–379. 10. Tan CS, Ouyang Y, Ruiz H, Sadda SR. Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2012;53:261–266.
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