MULTIMODAL IMAGING OF WHITE AND DARK WITHOUT PRESSURE FUNDUS LESIONS AMANI A. FAWZI, MD,* JARED S. NIELSEN,† ARANZAZU MATEO-MONTOYA,‡ THANAPONG SOMKIJRUNGROJ,§¶ HELEN K. LI,**††‡‡ JOHN GONZALES,§ MARTINE MAUGET-FAŸSSE‡ LEE M. JAMPOL, MD* Purpose: To describe multimodal imaging findings in patients with dark or white without pressure lesions of the fundus. Methods: Retrospective observational case series of 10 patients with white or dark without pressure lesions. We analyzed multimodal imaging using spectral domain optical coherence tomography, color and near-infrared fundus photography, and fundus autofluorescence imaging to explore the findings associated with these lesions. Results: All patients had geographic dark or white lesions on clinical examination and color photography, which were either hyporeflective or hyperreflective on near-infrared reflectance imaging, respectively. On optical coherence tomography, these lesions correlated with an abrupt change of the photoreceptor reflectivity, with relative hyporeflectivity of photoreceptor zones (ellipsoid and interdigitation zones, as well as outer segments) within the dark, and relative hyperreflectivity within white lesions. Ten patients underwent fundus autofluorescence, which showed well-defined zones of relative hypoautofluorescence within the lesion, compared with neighboring uninvolved regions, whether dark or white without pressure. In two patients who had a lesion combining white and dark without pressure, we observed the transition in photoreceptor reflectivity from the dark lesion (hyporeflective) to the white lesion (hyperreflective), relative to the surrounding retina. Conclusion: Both white and dark without pressure lesions are associated with changes in outer retinal reflectivity on optical coherence tomography, which occur in opposite directions compared with the surrounding unaffected areas. In the face of normal visual field testing to date, the clinical significance of this finding remains uncertain. Recognition of the optical coherence tomography appearance will help clinicians avoid unnecessary workup of these patients for outer retinal dystrophy or degeneration. RETINA 34:2376–2387, 2014
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single optical coherence tomography (OCT) case report,3 the prevalent clinical impression of white without pressure lesions has been that they are related to interface reflectivity changes at vitreoretinal interface. In this series, we use multimodal imaging to show that both white and dark lesions are associated with OCT changes at the level of the outer retina. Using the current data, we cannot rule out the possibility that these outer retinal reflectivity changes are induced by vitreous traction. Furthermore, we demonstrate that the relevant reflectivity change is not caused by photopigment, because both lesions demonstrate hypo-autofluorescence that is not subject to bleaching. Our results suggest that the reflectivity
ark without pressure lesions are asymptomatic, incidentally noted central to midperipheral fundus lesions that were originally reported in darkly pigmented patients with sickle retinopathy.1 Since the original report, this entity has been largely ignored and its histopathologic correlations remain unknown. Interestingly, despite the more common occurrence of white without pressure lesions first reported by Rutnin and Schepens2 in 1967 in the normal retinal periphery, the clinicopathologic correlations of this entity also remain unknown. In this study, we used multimodal imaging in 10, otherwise healthy, patients with mostly incidental findings of dark or white without pressure lesions. Until a recent
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change occurs at the level of the outer retina in both white and dark lesions, but in different directions, one being hyperreflective and the other hyporeflective on infrared reflectance and OCT imaging, respectively. Methods Institutional Review Board approval was obtained at Northwestern University (five cases), whereas it was waived in accordance with their respective requirements for reporting single case reports in the other participating institutions. Patient records were retrospectively reviewed and data abstracted for this report. All patients underwent multimodal imaging, including spectral domain OCT, color and nearinfrared fundus photography, and fundus autofluorescence imaging, as tolerated by the individual cases. Visual field testing was performed in one patient using Goldmann perimetry. Results Case 1 A 25-year-old asymptomatic, adopted African American woman was referred for evaluation of a peripheral fundus lesion in her right eye. This lesion had been first noted 3 years previously. The optometrist was concerned that it was becoming more prominent. She had a history of migraines and was myopic (spherical equivalent: −5.00 in her right eye, −5.50 in her left eye). Corrected visual acuity was 20/20 in each eye. Examination including confrontation visual fields was normal except for fundus findings in her right eye. Ophthalmoscopy revealed a flat discrete patch of darker retina with well-defined scalloped edges in the inferonasal periphery (Figure 1A). No vascular abnormalities were present, and no evidence of vitreous From the *Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; †Wolfe Eye Clinic, West Des Moines, Iowa; ‡Rothschild Foundation, Paris, France; §F. I. Proctor Foundation, University of California, San Francisco, California; ¶Uveitis Unit, Department of Ophthalmology, Chulalongkorn University, Bangkok, Thailand; **Department of Ophthalmology, Houston Methodist Hospital, Houston, Texas; and Departments of ††Ophthalmology, and ‡‡Radiation Oncology, Weill Cornell Medical College, Houston, Texas. Supported in part by an unrestricted grant from Research to Prevent Blindness Inc, New York, NY (Northwestern University) and a gift from Mary Dempsey and Kevin Hitzeman (L.M.J.). None of the authors have any financial/conflicting interests to disclose. Reprint requests: Lee M. Jampol, MD, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL; e-mail: [email protected]
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separation or traction was identified. The surrounding retina had a grayish cast. Spectral domain ocular coherence tomography (Figure 1B) revealed normal vitreoretinal interface and normal retinal and choroidal architecture in the patch of dark fundus. Scans centered on the border of the lesion demonstrated normal hyperreflectivity of the ellipsoid zone (inner segment and outer segment junction) outside the lesion, with a discrete transition to hyporeflectivity of the outer retinal bands within the dark fundus patch. No evidence of vitreous traction was noted. No change has been noted over 1 year of follow-up. Case 2 A 14-year-old Hispanic boy was referred for an incidental finding of retinal astrocytic hamartoma found during workup for a headache. The patient was otherwise healthy. Brain magnetic resonance imaging showed an arachnoid cyst, and concern for increased intracranial pressure prompted a retinal evaluation. The right fundus showed an astrocytic hamartoma along the inferior arcade, with an unrelated, well-defined area of dark without pressure outside the arcade (Figure 2A). Fundus autofluorescence showed intense hypo-autofluorescence within the lesion (Figure 2B). Optical coherence tomography through the astrocytic hamartoma confirmed its location in the retinal nerve fiber layer. Nearinfrared reflectance and OCT through the dark without pressure lesion showed abrupt transition to hyporeflective outer segments in the lesion, which did not change with OCT beam direction change (Figure 2, C and D). Case 3 A 12-year-old African American female was referred for evaluation of a possible choroidal nevus. The referring optometrist noted the finding 1 year ago and was concerned about possible enlargement. The eye and medical history were unremarkable. There was a 9- · 9-mm area of dark retina in the inferior posterior pole of her right eye with a distinct 360° border. Although darker than the surrounding retina, the absence of melanosis and presence of a sharp border suggested that the dark area was not a nevus. Hyporeflectivity of the ellipsoid zone on OCT, nearinfrared, and hypo-autofluorescence were seen in the dark retinal area (Figure 3). Case 4 A black 27-year-old African woman presented with complaints of blurry vision in the right eye for 1 week.
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Fig. 1. Case 1. A. Fundus montage demonstrating a dark without pressure fundus lesion of the inferonasal midperiphery of the right eye. B. Near-infrared reflectance shows decreased reflectivity within lesion. Optical coherence tomography scan through the temporal edge of lesion shows abrupt transition of photoreceptor reflectivity to hyporeflectivity.
Best-corrected visual acuity was 20/32 in her right eye and 20/20 in her left eye. Her medical history revealed thyroid cancer, which was treated with radiotherapy. Her ocular history included peripheral retinal tears, treated with argon laser. The patient was noted to have the multiple evanescent white dot syndrome in the right eye. This was confirmed by “en face” OCT showing disruption of the ellipsoid zone in the macula area of the right eye (not shown). The OCT scan showed a partial, shallow posterior vitreous detachment. The Goldmann visual field test of the right eye showed a cecocentral scotoma, which corresponded to her presenting complaint but was otherwise unremarkable. Fundus color photographs also revealed brown–red geographic areas outside the arcades in the right eye and nasal to disk in the left eye. These lesions corresponded to near-infrared hyporeflective zones, corresponding to spectral domain OCT photoreceptor hyporeflectivity seen in the corresponding scans (Figure 4, A–E). Full-field electroretinogram, positron emission tomography scan, uveitis laboratory workup, and hemoglobin electrophoresis were all within normal limits. One month after her initial visit, the central scotoma had disappeared, but she still had an enlarged blind spot. Her best-corrected visual acuity had improved to 20/20 in the right eye, along with normalization of the macular ellipsoid zone, consistent with resolution of her multiple evanescent white dot syndrome. Optical coherence tomography scans in the area of the extramacular dark lesions showed that the ellipsoid zone hyporeflectivity remained the same, matching with the infrared hyporeflective geographic areas. Autofluorescence imaging was repeated with bleaching, which showed these areas remained hypoautofluorescent and did not bleach compared with the surrounding region of
the fundus, which became hyperautofluorescent (Figure 4F). Repeat Goldmann visual field showed enlarged blind spot in the right eye, along with “dip” in the IIA isopter superior to fixation consistent with the original diagnosis of resolved multiple evanescent white dot syndrome, but otherwise normal in both eyes (Figure 4G). We performed patching of the eye for 4 hours, which did not change the reflectivity of the lesion, either on OCT or fundus imaging. Case 5 A 37-year-old asymptomatic, otherwise healthy African American man was referred for evaluation of a peripheral pigmented lesion in the left eye. Vision with a mild myopic correction was 20/25 in each eye. Ocular examination was normal in both eyes except a large well-defined dark patch in the superior temporal periphery of the fundus (Figure 5A). No other fundus abnormalities were noted. Fundus autofluorescence demonstrated a large hypoautofluorescent patch with sharply demarcated borders (Figure 5B). Spectral domain OCT demonstrated attenuation of the ellipsoid zone reflectance in the dark fundus lesion without any alteration of the vitreoretinal interface (Figure 5C). Case 6 A 16-year-old white girl was originally referred for evaluation of a darkly pigmented lesion in her right eye. The lesion in her right eye was consistent with congenital hypertrophy of the retinal pigment epithelium (not shown). She was also found to have an incidental white without pressure lesion in the preequatorial retina of the left eye (Figure 6A). Infrared reflectance imaging of the left eye in the region of white without pressure revealed a previously
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Fig. 2. Case 2. A. Color photograph highlights the dark without pressure lesion just outside the arcade of the left eye. Notably, the patient had an astrocytic hamartoma along the inferior arcade, which was the original reason for referral. B. Fundus autofluorescence (488 nm) shows well-defined hypoautofluorescence within the lesion. C. Infrared reflectance shows hyporeflectivity within the lesion. Horizontal OCT section through the top of the lesion shows transition from normal to hyporeflectivity, back to normal reflectivity at the photoreceptors. D. Vertical OCT section similarly shows hyporeflectivity within the lesion (the left side of the scan) that abruptly changes to hyperreflectivity, in the normal fundus, just outside the border of the lesion. The infrared reflectance photograph is slightly out of focus in this image, as evidence by the absence of light reflex and indistinct borders of retinal vessels, hence low contrast of the dark without pressure lesion, compared with (C).
unrecognized rim of dark without pressure posterior to the lesion (hyporeflectivity on infrared, Figure 6B). Optical coherence tomography showed that all the photoreceptor zones (ellipsoid and interdigitation zones and outer segments) showed a transition from mild hyperreflectivity (normal retina) to hyporeflectivity
(dark without pressure) to intense hyperreflectivity (white without pressure) (Figure 6B). Case 7 A 12-year-old white boy with a history of HLA-B27 anterior and intermediate uveitis was noted to have an
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Fig. 3. Case 3. A. Fundus photomontage of dark without pressure lesion. B. Spectral domain OCT vertical and (C) horizontal scans illustrating differences in the normal and dark retina, with decreased reflectivity of the photoreceptor bands. D. Hyporeflectivity is shown on near-infrared reflectance and (E) hypo-autofluoresence on fundus autofluorescence images.
incidental dark fundus lesion (Figure 7A). The patient had quiescent uveitis, treated with adalimumab. Fundus photography (Optos, Dunfermline, Scotland) showed dark geographic lesions, more prominent on green (532 nm) reflectance (Figure 7B), with mild hypoautofluorescence on green 532 nm autofluorescence (Figure 7C). Optical coherence tomography showed abrupt transition to hyporeflectivity of the outer retina at the level of ellipsoid and interdigitation zones (Figure 7D). Case 8 A 31-year-old white man with a history of myopia presented with flashes after blunt trauma to his left eye. He was found to have incidental areas of white without pressure in the retinal periphery (Figure 8A). Fundus autofluorescence showed hypoautofluorescence within the lesion (Figure 8B). Nearinfrared reflectance showed hyper-reflectance within lesion, whereas OCT through the lesions showed an increased hyperreflectivity at the level of the outer retina that began abruptly at the border of the lesion (Figure 8C). Case 9 A 20-year-old African American woman presented with unilateral increase in floaters. Dilated fundus
examination disclosed unilateral patches of peripheral white without pressure, with a surrounding border of darker lesions in the symptomatic right eye (Figure 9A). There was significant vitreous syneresis without the areas of clinical posterior vitreous detachment, tears, or holes. Fundus autofluorescence imaging revealed hypo-autofluorescence in both dark and white lesions (Figure 9B). The infrared reflectance showed transition from hyporeflectivity to hyperreflectivity within the dark and white lesions respectively, which correlated with similar transition on OCT in the outer photoreceptor lines, compared with the surrounding fundus (Figure 9C). Case 10 A 9-year-old Asian boy was referred by his optometrist who noted asymptomatic “dark lesions” in the fundus, which increased in size during follow-up. Dilated fundus examination revealed bilateral, nasal dark without pressure lesions. Review of fundus photographs (Optos) from referring optometrist revealed significant interim enlargement of the lesions over the duration of 9 months of follow-up (Figure 10, A–D). The lesions were better visualized on the green channel of these images (Figure 10, B and D). Optical coherence
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Fig. 4. Case 4. A and B. Wide-angle infrared reflectance of the right and left eyes show the dark without pressure lesion with relative hyporeflectivity within the lesion that lies nasal to the optic nerve and extends above and below the arcades. The fundus autofluorescence of both eyes show similar hypo-autofluorescence within the lesions. C. Infrared reflectance along the arcade highlights the hypo-reflectance within the lesion, whereas the OCT scan shows the transition to photoreceptor hyporeflectivity within the lesion at its temporal border. D. Optical coherence tomography just nasal to optic nerve shows normal photoreceptor reflectivity in the center of the scan that changes to hyporeflectivity above and below as it enters the superior and inferior edges of the lesion. E. A vertical OCT scan more nasal to (D), lying entirely within the lesion showing consistent hyporeflectivity at the level of photoreceptors. F. Effect of photobleaching on autofluorescence. A 20 · 20° fundus autofluorescence shows hypo-autofluorescence of the lesion. A wide-angle fundus autofluorescence obtained immediately afterward shows bleaching of the normal photoreceptor pigment, with hyper-autofluorescence in the macula, whereas the dark lesion shows relative resistance to photobleaching, compared with the surrounding retina. G. Goldman visual field of both eyes, showing normal isopters within the posterior pole of both eyes. The right eye has residual enlargement of the blind spot secondary to diagnosis of multiple evanescent white dot syndrome.
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Fig. 5. Case 5. A. Color photograph shows the geographic dark lesion of the superior temporal fundus of the left eye. B. Fundus autofluorescence shows hypo-autofluorescence within lesion. C. Infrared reflectance shows hypo-reflectance within lesion, whereas OCT shows decreased reflectivity of the photoreceptors within lesion.
tomography obtained through the lesions showed hyporeflectivity of the outer segments within the lesion, transitioning to normal reflectivity in unaffected regions (Figure 10E).
Discussion Since its original description by Nagpal et al1 in 1975, dark without pressure fundus lesions have been
Fig. 6. Case 6. A. Color fundus photograph shows peripheral temporal white without pressure that has a relatively darker posterior border, in the left eye. B. Infrared reflectance shows that the dark border of the lesion is relatively hyporeflective compared with the surrounding fundus, whereas the white without pressure area is relatively hyperreflective. The OCT scan shows a transition from normal photoreceptor reflectivity to relative hyporeflectivity (within dark without pressure), which further changes to abrupt hyperreflectivity within the white without pressure lesion. This hyperreflectivity appears more intense in reflectivity than the normal photoreceptors and possibly more intense and wider than the underlying retinal pigment epithelium.
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Fig. 7. Case 7. A. Wide-field color photograph shows a geographic dark lesion with sharply demarcated borders in the equatorial region of the temporal and superior fundus of the left eye. B. Green channel photograph (532 nm) highlighting the dark lesion in the temporal fundus. C. Green (532 nm) fundus autofluorescence shows mild hypo-autofluorescence relative to the surrounding fundus. D. Infrared reflectance shows relative hypo-reflectance within the dark lesion. Optical coherence tomography scan illustrates the abrupt transition to hyporeflectivity of the photoreceptor lines within the lesion, and return to normal reflectivity just outside the lesion.
largely ignored. The initial report included seven cases of brown fundus lesions in African American patients with various hemoglobinopathies (four with SS, two with SC, and one with hypertension and AA). The authors proposed the term “dark without pressure” because of the resemblance in shape to white without pressure fundus lesions. In the original article, these lesions were reported to be transient, change shape, and occasionally completely disappear over weeks. They hypothesized that these lesions represent altered reflex at the internal limiting membrane or retinal pigment epithelium but discounted the possibility that the lesions are islands of normal retina in an otherwise diffusely white without pressure fundus. In this report, we discount the currently prevailing hypothesis about both dark and white without pressure lesions, which postulates that they are caused by vitreoretinal interface abnormalities. Using OCT and multimodal imaging, we identify the location of these lesions at the level of outer retina and confirm the original suggestion that dark lesions may be related to white without pressure lesions. Similar to a recent white without pressure case report,3 OCT showed increased reflectivity of the ellipsoid and interdigitation zones in the white without pressure aspect, which transitioned to hyporeflectivity in the dark without pressure zone. Furthermore, we show for the first time that these dark lesions can occur in Caucasians and expand the spectrum of findings to show hypo-autofluorescence within both dark and white without pressure lesions.
To further explore the potential origin of this lesion, we performed spectral domain OCT. All patients had an abrupt transition to hyporeflectivity of the ellipsoid and outer segments of the photoreceptors within the dark fundus lesion. To exclude the potential for artifact related to OCT beam direction causing these lesions, we performed several vertical and horizontal OCT sections on Patients 2 to 8. All of these OCT sections showed the same abrupt transition to hyporeflectivity at the level of photoreceptors coinciding with the border of the dark lesion, or hyperreflectivity in the white lesions, confirming that these defects are not caused by artifact (Figure 2, C and D; Figure 3, B and C). We saw no OCT alterations of the overlying vitreous, vitreoretinal interface, or inner retina that could explain these outer retinal OCT findings. Additionally, in two patients who had a lesion with both white and dark without pressure, we showed that these lesions have relatively increased or decreased reflectivity at the level of the photoreceptors, respectively compared with the adjacent unaffected fundus having intermediate reflectivity (Figures 6B and 9C). Visual field testing in Case 4, which had the largest lesion, did not show any visual defect, which suggests that dark without pressure lesions are associated with structural, but perhaps not functional, changes at the level of the photoreceptors. Although the specific biochemical or structural etiology of the outer retinal alteration remains unknown, we propose that these findings are related
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Fig. 8. Case 8. A. Color fundus photograph shows peripheral intense white without pressure lesions inferotemporally in the left eye of the patient. B. Fundus autofluorescence shows relative hypo-autofluorescence compared with the surrounding retina. C. Infrared reflectance shows relative hyperreflectivity within lesion, whereas OCT scan shows intense hyperreflectivity at the level of the photoreceptors that abruptly transitions to hyporeflectivity at the border of the normal surrounding fundus.
to the presence of photopigment with different density or spectral range within these lesions, compared with the rest of the fundus. Specifically, this focal change in white and dark lesions is associated with photopigment that absorbs short-wavelength light more effectively. This explains the increased filtering occurring in 488 nm fundus autofluorescence, leading to hypo-autofluorescence in both lesions (Figures 2B, 3E, 4F, and 8B), and the increased visibility (dark appearance) of these lesions in red-free and 532 nm fundus photography (Figures 7B and 10, B and D). Interestingly, the lesion in Case 4 showed almost no bleaching in blue light compared with the surrounding fundus (Figure 4F). The difference in OCT appearance may be related to differences in the scattering properties of these abnormal photopigments to infrared light. Interestingly, these lesions appear to have opposite reflectivity in near-infrared reflectance,
although less prominent compared with their OCT appearance (a measure of their ability to scatter infrared light) in relationship to the surrounding unaffected fundus (Figures 6B and 8C). Our hypothesis is also based on similar, although reversible, outer retinal finding on OCT in the Mizuo–Nakamura phenomenon. In this condition, the golden tapetal sheen noted in light adapted fundus is associated with a brightly hyperreflective zone in the outer segments on OCT, opposite to patients with dark without pressure fundus lesions. This hyperreflectivity is replaced by significant hyporeflectivity in the darkadapted state, with disappearance of the golden sheen, which is similar to dark without pressure.4 The origin of the tapetal sheen as a result of increased reflectance at the photoreceptor outer segments has also been shown using psychophysical and detailed densitometry studies in carriers of X-linked retinoschisis.5 The
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Fig. 9. Case 9. A. Color fundus photograph shows peripheral intense white without pressure lesions inferotemporally in the right eye of the patient, with a surrounding border of dark without pressure. B. Fundus autofluorescence shows relative hypo-autofluorescence compared with the surrounding retina. C. Optical coherence tomography scan shows intense hyperreflectivity at the level of the inner segments and ellipsoid zone of photoreceptors that abruptly transitions to relative hyporeflectivity at the dark border of the lesion, which in turn transitions to normal reflectivity in the surrounding normal retina.
exact cause is greatly debated. Previously proposed explanations for the Mizuo phenomenon include K+ accumulation (or decrease) in the outer retina because of a defect in Müller cells,6 defective recycling of photoreceptor outer segments,5 or a cone defect.7 It is possible that some of these mechanisms may be relevant to dark and white without pressure lesions, except perhaps the cone-related mechanism, given that the preferential location of these dark and white without pressure lesions is in the midperiphery. Although the visual consequences of dark without pressure lesions are unknown, we believe that, based on their similarity to the OCT appearance of the darkadapted Mizuo–Nakamura, they may be associated with focal defects in photoreceptor structure. Unlike Oguchi disease, where patients have a generalized genetically determined defect in photoreceptor recovery, the isolated defects in these dark lesions are likely too circumscribed and too subtle to be of any clinical significance or cause generalized full-field electroretinogram changes. Patient 4, with bilateral lesions, the
largest in size in this series, had a normal full-field electroretinogram and no visual field defects related to these lesions on Goldmann perimetry (Figure 4G). Any relationship of dark without pressure to sickle cell disease seems unlikely. Although most of our patients have not undergone testing for sickle cell hemoglobinopathy, two patients had normal hemoglobin electrophoresis. Based on the racial mix of our patients (6 of 8 with dark without pressure were darkly pigmented) and previously reported cases,1 it seems likely that fundus pigmentation plays a role in the occurrence, or perhaps more likely in the clinician’s ability to detect these lesions.
Conclusion Dark without pressure fundus lesions demonstrate localized hyporeflectivity of the outer segment and ellipsoid zones on OCT, whereas white without pressure lesions show hyperreflectivity in these
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Fig. 10. Case 10. A. Wide-field color photograph of the right eye shows two separate, geographic dark lesions with distinct borders. B. Green channel images reveal better visualization of the lesions. C. Repeat imaging at 9 months shows significant enlargement of both lesions in their equatorial extent, as well as closer to the optic nerve. D. Green channel images highlight the enlargement of the borders. E. Vertical OCT scan that straddles the two geographic lesions and shows transition of outer photoreceptor reflectivity from hyporeflectivity within lesion, to normal reflectivity between lesions, then back to hyporeflectivity in the second lesion.
structures, thus discounting both lesions’ relationship to vitreoretinal interface abnormalities. Based on our findings, dark and white without pressure lesions appear to represent the opposite ends of a spectrum of photoreceptor reflectivity on OCT, with “normal” photoreceptor reflectivity being in the middle of that spectrum. The functional significance and pathogenesis of these outer retinal changes remain unknown, and may be related to vitreous traction in these areas, but so far we have not detected functional changes. Similarly, no functional defects have been reported previously in patients with white without pressure
lesions. Dark without pressure fundus lesions seem to be more common in patients of darkly pigmented complexion, have been reported to be evanescent and as we showed can be migratory, and are likely of little consequence from a vision standpoint. Their tendency to enlarge or migrate may cause alarm and incite referrals and additional workup, as in Patient 10 in this series. Although the role of vitreous traction as a precipitating factor for these lesions cannot be ruled out in our study, further diagnostic assessment including swept-source OCT, microperimetry, densitometry, or
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spectral electroretinogram may add further to our understanding of these entities. Key words: dark without pressure, white without pressure, optical coherence tomography, fundus autofluorescence. References 1. Nagpal KC, Goldberg MF, Asdourian G, et al. Dark-withoutpressure fundus lesions. Br J Ophthalmol 1975;59:476–479. 2. Rutnin U, Schepens CL. Fundus appearance in normal eyes. IV. Retinal breaks and other findings. Am J Ophthalmol 1967;64: 1063–1078.
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3. Diaz RI, Sigler EJ, Randolph JC, et al. Spectral domain optical coherence tomography characteristics of white-without-pressure. Retina 2013. 4. Takada M, Otani A, Ogino K, Yoshimura N. Spectral-domain optical coherence tomography findings in the Mizuo-Nakamura phenomenon of Oguchi disease. Retina 2011;31:626–628. 5. Berendschot TT, DeLint PJ, van Norren D. Origin of tapetal-like reflexes in carriers of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 1996;37:2716–2723. 6. de Jong PT, Zrenner E, van Meel GJ, et al. Mizuo phenomenon in X-linked retinoschisis. Pathogenesis of the Mizuo phenomenon. Arch Ophthalmol 1991;109:1104–1108. 7. Cideciyan AV, Jacobson SG. Image analysis of the tapetal-like reflex in carriers of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 1994;35:3812–3824.
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single optical coherence tomography (OCT) case report,3 the prevalent clinical impression of white without pressure lesions has been that they are related to interface reflectivity changes at vitreoretinal interface. In this series, we use multimodal imaging to show that both white and dark lesions are associated with OCT changes at the level of the outer retina. Using the current data, we cannot rule out the possibility that these outer retinal reflectivity changes are induced by vitreous traction. Furthermore, we demonstrate that the relevant reflectivity change is not caused by photopigment, because both lesions demonstrate hypo-autofluorescence that is not subject to bleaching. Our results suggest that the reflectivity
ark without pressure lesions are asymptomatic, incidentally noted central to midperipheral fundus lesions that were originally reported in darkly pigmented patients with sickle retinopathy.1 Since the original report, this entity has been largely ignored and its histopathologic correlations remain unknown. Interestingly, despite the more common occurrence of white without pressure lesions first reported by Rutnin and Schepens2 in 1967 in the normal retinal periphery, the clinicopathologic correlations of this entity also remain unknown. In this study, we used multimodal imaging in 10, otherwise healthy, patients with mostly incidental findings of dark or white without pressure lesions. Until a recent
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change occurs at the level of the outer retina in both white and dark lesions, but in different directions, one being hyperreflective and the other hyporeflective on infrared reflectance and OCT imaging, respectively. Methods Institutional Review Board approval was obtained at Northwestern University (five cases), whereas it was waived in accordance with their respective requirements for reporting single case reports in the other participating institutions. Patient records were retrospectively reviewed and data abstracted for this report. All patients underwent multimodal imaging, including spectral domain OCT, color and nearinfrared fundus photography, and fundus autofluorescence imaging, as tolerated by the individual cases. Visual field testing was performed in one patient using Goldmann perimetry. Results Case 1 A 25-year-old asymptomatic, adopted African American woman was referred for evaluation of a peripheral fundus lesion in her right eye. This lesion had been first noted 3 years previously. The optometrist was concerned that it was becoming more prominent. She had a history of migraines and was myopic (spherical equivalent: −5.00 in her right eye, −5.50 in her left eye). Corrected visual acuity was 20/20 in each eye. Examination including confrontation visual fields was normal except for fundus findings in her right eye. Ophthalmoscopy revealed a flat discrete patch of darker retina with well-defined scalloped edges in the inferonasal periphery (Figure 1A). No vascular abnormalities were present, and no evidence of vitreous From the *Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; †Wolfe Eye Clinic, West Des Moines, Iowa; ‡Rothschild Foundation, Paris, France; §F. I. Proctor Foundation, University of California, San Francisco, California; ¶Uveitis Unit, Department of Ophthalmology, Chulalongkorn University, Bangkok, Thailand; **Department of Ophthalmology, Houston Methodist Hospital, Houston, Texas; and Departments of ††Ophthalmology, and ‡‡Radiation Oncology, Weill Cornell Medical College, Houston, Texas. Supported in part by an unrestricted grant from Research to Prevent Blindness Inc, New York, NY (Northwestern University) and a gift from Mary Dempsey and Kevin Hitzeman (L.M.J.). None of the authors have any financial/conflicting interests to disclose. Reprint requests: Lee M. Jampol, MD, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL; e-mail: [email protected]
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separation or traction was identified. The surrounding retina had a grayish cast. Spectral domain ocular coherence tomography (Figure 1B) revealed normal vitreoretinal interface and normal retinal and choroidal architecture in the patch of dark fundus. Scans centered on the border of the lesion demonstrated normal hyperreflectivity of the ellipsoid zone (inner segment and outer segment junction) outside the lesion, with a discrete transition to hyporeflectivity of the outer retinal bands within the dark fundus patch. No evidence of vitreous traction was noted. No change has been noted over 1 year of follow-up. Case 2 A 14-year-old Hispanic boy was referred for an incidental finding of retinal astrocytic hamartoma found during workup for a headache. The patient was otherwise healthy. Brain magnetic resonance imaging showed an arachnoid cyst, and concern for increased intracranial pressure prompted a retinal evaluation. The right fundus showed an astrocytic hamartoma along the inferior arcade, with an unrelated, well-defined area of dark without pressure outside the arcade (Figure 2A). Fundus autofluorescence showed intense hypo-autofluorescence within the lesion (Figure 2B). Optical coherence tomography through the astrocytic hamartoma confirmed its location in the retinal nerve fiber layer. Nearinfrared reflectance and OCT through the dark without pressure lesion showed abrupt transition to hyporeflective outer segments in the lesion, which did not change with OCT beam direction change (Figure 2, C and D). Case 3 A 12-year-old African American female was referred for evaluation of a possible choroidal nevus. The referring optometrist noted the finding 1 year ago and was concerned about possible enlargement. The eye and medical history were unremarkable. There was a 9- · 9-mm area of dark retina in the inferior posterior pole of her right eye with a distinct 360° border. Although darker than the surrounding retina, the absence of melanosis and presence of a sharp border suggested that the dark area was not a nevus. Hyporeflectivity of the ellipsoid zone on OCT, nearinfrared, and hypo-autofluorescence were seen in the dark retinal area (Figure 3). Case 4 A black 27-year-old African woman presented with complaints of blurry vision in the right eye for 1 week.
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Fig. 1. Case 1. A. Fundus montage demonstrating a dark without pressure fundus lesion of the inferonasal midperiphery of the right eye. B. Near-infrared reflectance shows decreased reflectivity within lesion. Optical coherence tomography scan through the temporal edge of lesion shows abrupt transition of photoreceptor reflectivity to hyporeflectivity.
Best-corrected visual acuity was 20/32 in her right eye and 20/20 in her left eye. Her medical history revealed thyroid cancer, which was treated with radiotherapy. Her ocular history included peripheral retinal tears, treated with argon laser. The patient was noted to have the multiple evanescent white dot syndrome in the right eye. This was confirmed by “en face” OCT showing disruption of the ellipsoid zone in the macula area of the right eye (not shown). The OCT scan showed a partial, shallow posterior vitreous detachment. The Goldmann visual field test of the right eye showed a cecocentral scotoma, which corresponded to her presenting complaint but was otherwise unremarkable. Fundus color photographs also revealed brown–red geographic areas outside the arcades in the right eye and nasal to disk in the left eye. These lesions corresponded to near-infrared hyporeflective zones, corresponding to spectral domain OCT photoreceptor hyporeflectivity seen in the corresponding scans (Figure 4, A–E). Full-field electroretinogram, positron emission tomography scan, uveitis laboratory workup, and hemoglobin electrophoresis were all within normal limits. One month after her initial visit, the central scotoma had disappeared, but she still had an enlarged blind spot. Her best-corrected visual acuity had improved to 20/20 in the right eye, along with normalization of the macular ellipsoid zone, consistent with resolution of her multiple evanescent white dot syndrome. Optical coherence tomography scans in the area of the extramacular dark lesions showed that the ellipsoid zone hyporeflectivity remained the same, matching with the infrared hyporeflective geographic areas. Autofluorescence imaging was repeated with bleaching, which showed these areas remained hypoautofluorescent and did not bleach compared with the surrounding region of
the fundus, which became hyperautofluorescent (Figure 4F). Repeat Goldmann visual field showed enlarged blind spot in the right eye, along with “dip” in the IIA isopter superior to fixation consistent with the original diagnosis of resolved multiple evanescent white dot syndrome, but otherwise normal in both eyes (Figure 4G). We performed patching of the eye for 4 hours, which did not change the reflectivity of the lesion, either on OCT or fundus imaging. Case 5 A 37-year-old asymptomatic, otherwise healthy African American man was referred for evaluation of a peripheral pigmented lesion in the left eye. Vision with a mild myopic correction was 20/25 in each eye. Ocular examination was normal in both eyes except a large well-defined dark patch in the superior temporal periphery of the fundus (Figure 5A). No other fundus abnormalities were noted. Fundus autofluorescence demonstrated a large hypoautofluorescent patch with sharply demarcated borders (Figure 5B). Spectral domain OCT demonstrated attenuation of the ellipsoid zone reflectance in the dark fundus lesion without any alteration of the vitreoretinal interface (Figure 5C). Case 6 A 16-year-old white girl was originally referred for evaluation of a darkly pigmented lesion in her right eye. The lesion in her right eye was consistent with congenital hypertrophy of the retinal pigment epithelium (not shown). She was also found to have an incidental white without pressure lesion in the preequatorial retina of the left eye (Figure 6A). Infrared reflectance imaging of the left eye in the region of white without pressure revealed a previously
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Fig. 2. Case 2. A. Color photograph highlights the dark without pressure lesion just outside the arcade of the left eye. Notably, the patient had an astrocytic hamartoma along the inferior arcade, which was the original reason for referral. B. Fundus autofluorescence (488 nm) shows well-defined hypoautofluorescence within the lesion. C. Infrared reflectance shows hyporeflectivity within the lesion. Horizontal OCT section through the top of the lesion shows transition from normal to hyporeflectivity, back to normal reflectivity at the photoreceptors. D. Vertical OCT section similarly shows hyporeflectivity within the lesion (the left side of the scan) that abruptly changes to hyperreflectivity, in the normal fundus, just outside the border of the lesion. The infrared reflectance photograph is slightly out of focus in this image, as evidence by the absence of light reflex and indistinct borders of retinal vessels, hence low contrast of the dark without pressure lesion, compared with (C).
unrecognized rim of dark without pressure posterior to the lesion (hyporeflectivity on infrared, Figure 6B). Optical coherence tomography showed that all the photoreceptor zones (ellipsoid and interdigitation zones and outer segments) showed a transition from mild hyperreflectivity (normal retina) to hyporeflectivity
(dark without pressure) to intense hyperreflectivity (white without pressure) (Figure 6B). Case 7 A 12-year-old white boy with a history of HLA-B27 anterior and intermediate uveitis was noted to have an
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Fig. 3. Case 3. A. Fundus photomontage of dark without pressure lesion. B. Spectral domain OCT vertical and (C) horizontal scans illustrating differences in the normal and dark retina, with decreased reflectivity of the photoreceptor bands. D. Hyporeflectivity is shown on near-infrared reflectance and (E) hypo-autofluoresence on fundus autofluorescence images.
incidental dark fundus lesion (Figure 7A). The patient had quiescent uveitis, treated with adalimumab. Fundus photography (Optos, Dunfermline, Scotland) showed dark geographic lesions, more prominent on green (532 nm) reflectance (Figure 7B), with mild hypoautofluorescence on green 532 nm autofluorescence (Figure 7C). Optical coherence tomography showed abrupt transition to hyporeflectivity of the outer retina at the level of ellipsoid and interdigitation zones (Figure 7D). Case 8 A 31-year-old white man with a history of myopia presented with flashes after blunt trauma to his left eye. He was found to have incidental areas of white without pressure in the retinal periphery (Figure 8A). Fundus autofluorescence showed hypoautofluorescence within the lesion (Figure 8B). Nearinfrared reflectance showed hyper-reflectance within lesion, whereas OCT through the lesions showed an increased hyperreflectivity at the level of the outer retina that began abruptly at the border of the lesion (Figure 8C). Case 9 A 20-year-old African American woman presented with unilateral increase in floaters. Dilated fundus
examination disclosed unilateral patches of peripheral white without pressure, with a surrounding border of darker lesions in the symptomatic right eye (Figure 9A). There was significant vitreous syneresis without the areas of clinical posterior vitreous detachment, tears, or holes. Fundus autofluorescence imaging revealed hypo-autofluorescence in both dark and white lesions (Figure 9B). The infrared reflectance showed transition from hyporeflectivity to hyperreflectivity within the dark and white lesions respectively, which correlated with similar transition on OCT in the outer photoreceptor lines, compared with the surrounding fundus (Figure 9C). Case 10 A 9-year-old Asian boy was referred by his optometrist who noted asymptomatic “dark lesions” in the fundus, which increased in size during follow-up. Dilated fundus examination revealed bilateral, nasal dark without pressure lesions. Review of fundus photographs (Optos) from referring optometrist revealed significant interim enlargement of the lesions over the duration of 9 months of follow-up (Figure 10, A–D). The lesions were better visualized on the green channel of these images (Figure 10, B and D). Optical coherence
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Fig. 4. Case 4. A and B. Wide-angle infrared reflectance of the right and left eyes show the dark without pressure lesion with relative hyporeflectivity within the lesion that lies nasal to the optic nerve and extends above and below the arcades. The fundus autofluorescence of both eyes show similar hypo-autofluorescence within the lesions. C. Infrared reflectance along the arcade highlights the hypo-reflectance within the lesion, whereas the OCT scan shows the transition to photoreceptor hyporeflectivity within the lesion at its temporal border. D. Optical coherence tomography just nasal to optic nerve shows normal photoreceptor reflectivity in the center of the scan that changes to hyporeflectivity above and below as it enters the superior and inferior edges of the lesion. E. A vertical OCT scan more nasal to (D), lying entirely within the lesion showing consistent hyporeflectivity at the level of photoreceptors. F. Effect of photobleaching on autofluorescence. A 20 · 20° fundus autofluorescence shows hypo-autofluorescence of the lesion. A wide-angle fundus autofluorescence obtained immediately afterward shows bleaching of the normal photoreceptor pigment, with hyper-autofluorescence in the macula, whereas the dark lesion shows relative resistance to photobleaching, compared with the surrounding retina. G. Goldman visual field of both eyes, showing normal isopters within the posterior pole of both eyes. The right eye has residual enlargement of the blind spot secondary to diagnosis of multiple evanescent white dot syndrome.
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Fig. 5. Case 5. A. Color photograph shows the geographic dark lesion of the superior temporal fundus of the left eye. B. Fundus autofluorescence shows hypo-autofluorescence within lesion. C. Infrared reflectance shows hypo-reflectance within lesion, whereas OCT shows decreased reflectivity of the photoreceptors within lesion.
tomography obtained through the lesions showed hyporeflectivity of the outer segments within the lesion, transitioning to normal reflectivity in unaffected regions (Figure 10E).
Discussion Since its original description by Nagpal et al1 in 1975, dark without pressure fundus lesions have been
Fig. 6. Case 6. A. Color fundus photograph shows peripheral temporal white without pressure that has a relatively darker posterior border, in the left eye. B. Infrared reflectance shows that the dark border of the lesion is relatively hyporeflective compared with the surrounding fundus, whereas the white without pressure area is relatively hyperreflective. The OCT scan shows a transition from normal photoreceptor reflectivity to relative hyporeflectivity (within dark without pressure), which further changes to abrupt hyperreflectivity within the white without pressure lesion. This hyperreflectivity appears more intense in reflectivity than the normal photoreceptors and possibly more intense and wider than the underlying retinal pigment epithelium.
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Fig. 7. Case 7. A. Wide-field color photograph shows a geographic dark lesion with sharply demarcated borders in the equatorial region of the temporal and superior fundus of the left eye. B. Green channel photograph (532 nm) highlighting the dark lesion in the temporal fundus. C. Green (532 nm) fundus autofluorescence shows mild hypo-autofluorescence relative to the surrounding fundus. D. Infrared reflectance shows relative hypo-reflectance within the dark lesion. Optical coherence tomography scan illustrates the abrupt transition to hyporeflectivity of the photoreceptor lines within the lesion, and return to normal reflectivity just outside the lesion.
largely ignored. The initial report included seven cases of brown fundus lesions in African American patients with various hemoglobinopathies (four with SS, two with SC, and one with hypertension and AA). The authors proposed the term “dark without pressure” because of the resemblance in shape to white without pressure fundus lesions. In the original article, these lesions were reported to be transient, change shape, and occasionally completely disappear over weeks. They hypothesized that these lesions represent altered reflex at the internal limiting membrane or retinal pigment epithelium but discounted the possibility that the lesions are islands of normal retina in an otherwise diffusely white without pressure fundus. In this report, we discount the currently prevailing hypothesis about both dark and white without pressure lesions, which postulates that they are caused by vitreoretinal interface abnormalities. Using OCT and multimodal imaging, we identify the location of these lesions at the level of outer retina and confirm the original suggestion that dark lesions may be related to white without pressure lesions. Similar to a recent white without pressure case report,3 OCT showed increased reflectivity of the ellipsoid and interdigitation zones in the white without pressure aspect, which transitioned to hyporeflectivity in the dark without pressure zone. Furthermore, we show for the first time that these dark lesions can occur in Caucasians and expand the spectrum of findings to show hypo-autofluorescence within both dark and white without pressure lesions.
To further explore the potential origin of this lesion, we performed spectral domain OCT. All patients had an abrupt transition to hyporeflectivity of the ellipsoid and outer segments of the photoreceptors within the dark fundus lesion. To exclude the potential for artifact related to OCT beam direction causing these lesions, we performed several vertical and horizontal OCT sections on Patients 2 to 8. All of these OCT sections showed the same abrupt transition to hyporeflectivity at the level of photoreceptors coinciding with the border of the dark lesion, or hyperreflectivity in the white lesions, confirming that these defects are not caused by artifact (Figure 2, C and D; Figure 3, B and C). We saw no OCT alterations of the overlying vitreous, vitreoretinal interface, or inner retina that could explain these outer retinal OCT findings. Additionally, in two patients who had a lesion with both white and dark without pressure, we showed that these lesions have relatively increased or decreased reflectivity at the level of the photoreceptors, respectively compared with the adjacent unaffected fundus having intermediate reflectivity (Figures 6B and 9C). Visual field testing in Case 4, which had the largest lesion, did not show any visual defect, which suggests that dark without pressure lesions are associated with structural, but perhaps not functional, changes at the level of the photoreceptors. Although the specific biochemical or structural etiology of the outer retinal alteration remains unknown, we propose that these findings are related
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Fig. 8. Case 8. A. Color fundus photograph shows peripheral intense white without pressure lesions inferotemporally in the left eye of the patient. B. Fundus autofluorescence shows relative hypo-autofluorescence compared with the surrounding retina. C. Infrared reflectance shows relative hyperreflectivity within lesion, whereas OCT scan shows intense hyperreflectivity at the level of the photoreceptors that abruptly transitions to hyporeflectivity at the border of the normal surrounding fundus.
to the presence of photopigment with different density or spectral range within these lesions, compared with the rest of the fundus. Specifically, this focal change in white and dark lesions is associated with photopigment that absorbs short-wavelength light more effectively. This explains the increased filtering occurring in 488 nm fundus autofluorescence, leading to hypo-autofluorescence in both lesions (Figures 2B, 3E, 4F, and 8B), and the increased visibility (dark appearance) of these lesions in red-free and 532 nm fundus photography (Figures 7B and 10, B and D). Interestingly, the lesion in Case 4 showed almost no bleaching in blue light compared with the surrounding fundus (Figure 4F). The difference in OCT appearance may be related to differences in the scattering properties of these abnormal photopigments to infrared light. Interestingly, these lesions appear to have opposite reflectivity in near-infrared reflectance,
although less prominent compared with their OCT appearance (a measure of their ability to scatter infrared light) in relationship to the surrounding unaffected fundus (Figures 6B and 8C). Our hypothesis is also based on similar, although reversible, outer retinal finding on OCT in the Mizuo–Nakamura phenomenon. In this condition, the golden tapetal sheen noted in light adapted fundus is associated with a brightly hyperreflective zone in the outer segments on OCT, opposite to patients with dark without pressure fundus lesions. This hyperreflectivity is replaced by significant hyporeflectivity in the darkadapted state, with disappearance of the golden sheen, which is similar to dark without pressure.4 The origin of the tapetal sheen as a result of increased reflectance at the photoreceptor outer segments has also been shown using psychophysical and detailed densitometry studies in carriers of X-linked retinoschisis.5 The
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Fig. 9. Case 9. A. Color fundus photograph shows peripheral intense white without pressure lesions inferotemporally in the right eye of the patient, with a surrounding border of dark without pressure. B. Fundus autofluorescence shows relative hypo-autofluorescence compared with the surrounding retina. C. Optical coherence tomography scan shows intense hyperreflectivity at the level of the inner segments and ellipsoid zone of photoreceptors that abruptly transitions to relative hyporeflectivity at the dark border of the lesion, which in turn transitions to normal reflectivity in the surrounding normal retina.
exact cause is greatly debated. Previously proposed explanations for the Mizuo phenomenon include K+ accumulation (or decrease) in the outer retina because of a defect in Müller cells,6 defective recycling of photoreceptor outer segments,5 or a cone defect.7 It is possible that some of these mechanisms may be relevant to dark and white without pressure lesions, except perhaps the cone-related mechanism, given that the preferential location of these dark and white without pressure lesions is in the midperiphery. Although the visual consequences of dark without pressure lesions are unknown, we believe that, based on their similarity to the OCT appearance of the darkadapted Mizuo–Nakamura, they may be associated with focal defects in photoreceptor structure. Unlike Oguchi disease, where patients have a generalized genetically determined defect in photoreceptor recovery, the isolated defects in these dark lesions are likely too circumscribed and too subtle to be of any clinical significance or cause generalized full-field electroretinogram changes. Patient 4, with bilateral lesions, the
largest in size in this series, had a normal full-field electroretinogram and no visual field defects related to these lesions on Goldmann perimetry (Figure 4G). Any relationship of dark without pressure to sickle cell disease seems unlikely. Although most of our patients have not undergone testing for sickle cell hemoglobinopathy, two patients had normal hemoglobin electrophoresis. Based on the racial mix of our patients (6 of 8 with dark without pressure were darkly pigmented) and previously reported cases,1 it seems likely that fundus pigmentation plays a role in the occurrence, or perhaps more likely in the clinician’s ability to detect these lesions.
Conclusion Dark without pressure fundus lesions demonstrate localized hyporeflectivity of the outer segment and ellipsoid zones on OCT, whereas white without pressure lesions show hyperreflectivity in these
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Fig. 10. Case 10. A. Wide-field color photograph of the right eye shows two separate, geographic dark lesions with distinct borders. B. Green channel images reveal better visualization of the lesions. C. Repeat imaging at 9 months shows significant enlargement of both lesions in their equatorial extent, as well as closer to the optic nerve. D. Green channel images highlight the enlargement of the borders. E. Vertical OCT scan that straddles the two geographic lesions and shows transition of outer photoreceptor reflectivity from hyporeflectivity within lesion, to normal reflectivity between lesions, then back to hyporeflectivity in the second lesion.
structures, thus discounting both lesions’ relationship to vitreoretinal interface abnormalities. Based on our findings, dark and white without pressure lesions appear to represent the opposite ends of a spectrum of photoreceptor reflectivity on OCT, with “normal” photoreceptor reflectivity being in the middle of that spectrum. The functional significance and pathogenesis of these outer retinal changes remain unknown, and may be related to vitreous traction in these areas, but so far we have not detected functional changes. Similarly, no functional defects have been reported previously in patients with white without pressure
lesions. Dark without pressure fundus lesions seem to be more common in patients of darkly pigmented complexion, have been reported to be evanescent and as we showed can be migratory, and are likely of little consequence from a vision standpoint. Their tendency to enlarge or migrate may cause alarm and incite referrals and additional workup, as in Patient 10 in this series. Although the role of vitreous traction as a precipitating factor for these lesions cannot be ruled out in our study, further diagnostic assessment including swept-source OCT, microperimetry, densitometry, or
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spectral electroretinogram may add further to our understanding of these entities. Key words: dark without pressure, white without pressure, optical coherence tomography, fundus autofluorescence. References 1. Nagpal KC, Goldberg MF, Asdourian G, et al. Dark-withoutpressure fundus lesions. Br J Ophthalmol 1975;59:476–479. 2. Rutnin U, Schepens CL. Fundus appearance in normal eyes. IV. Retinal breaks and other findings. Am J Ophthalmol 1967;64: 1063–1078.
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3. Diaz RI, Sigler EJ, Randolph JC, et al. Spectral domain optical coherence tomography characteristics of white-without-pressure. Retina 2013. 4. Takada M, Otani A, Ogino K, Yoshimura N. Spectral-domain optical coherence tomography findings in the Mizuo-Nakamura phenomenon of Oguchi disease. Retina 2011;31:626–628. 5. Berendschot TT, DeLint PJ, van Norren D. Origin of tapetal-like reflexes in carriers of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 1996;37:2716–2723. 6. de Jong PT, Zrenner E, van Meel GJ, et al. Mizuo phenomenon in X-linked retinoschisis. Pathogenesis of the Mizuo phenomenon. Arch Ophthalmol 1991;109:1104–1108. 7. Cideciyan AV, Jacobson SG. Image analysis of the tapetal-like reflex in carriers of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 1994;35:3812–3824.
