Grand Rounds at the New England Eye CenterPublication Exclusive

Patient presents with acute unilateral dark spot in vision

At presentation, BCVA was decreased in the right eye, which also had a relative afferent pupillary defect.

An 18-year-old woman presented to our clinic with a complaint of 3 days of decreased vision in her right eye. She reported that the vision in her right eye had appeared “washed out” for 2 days, followed by the development of a dark spot in her central vision. She described mild irritation of the right eye but denied any eye pain, pain with eye movement, redness, photophobia, photopsias or ocular trauma. She reported that her younger siblings had a flu-like illness several weeks before the onset of her symptoms but that she herself had not been ill. Her ocular history included only myopia. She had no medical history. She was on no medications.

Examination

At the time of presentation, best corrected visual acuity was 20/80 in the right eye and 20/25 in the left eye. IOP was within normal limits. Pupils were round and reactive to light in both eyes with a 1+ relative afferent pupillary defect noted in the right eye. On Ishihara color plate testing, the patient correctly identified only the control plate with the right eye and 10/10 plates with the left eye. Slit lamp exam was unremarkable, and dilated funduscopy demonstrated normal-appearing fundi in both eyes. Both optic nerves were found to have 0.1 cup-to-disc ratio with no edema. Humphrey visual field testing revealed a small paracentral scotoma in the right eye, which was also seen on Amsler grid testing. The visual field was full in the left eye.

Given the acute onset, normal-appearing fundus, afferent pupillary defect and decreased color vision, concern was initially for a primary process of the optic nerve, with a suspicion for retrobulbar optic neuritis. An MRI of the orbits was obtained and demonstrated right optic nerve hyperintensity without enhancement as well as a right carotid artery flow void, possibly representing a dissection, thrombosis or congenital variant. Although a carotid dissection would be unlikely to result in an isolated ipsilateral optic neuropathy, the patient underwent urgent MRA of the head and neck to exclude emergent diagnoses. The MRA revealed congenital hypoplasia of the right internal carotid, a normal variant and incidental finding.

Figure 1. Spectral-domain OCT of the macula of the right eye showing disruption and effacement of the outer retina at the level of the inner segment/outer segment, thickening at the level of the retinal pigment epithelium and trace subretinal fluid (a). Normal foveal contour and retinal architecture was seen in the left eye (b).

Images: Tawse KL, Waheed NK

Figure 2. Fundus photography of the right eye showing a deep yellowish discoloration superior to the fovea in the right eye. A normal fundus was observed in the left eye.

Figure 3. Early patchy hypofluorescence and hyperfluorescence were seen superior to the fovea on fluorescein angiography in the right eye with late patchy staining in the same area and central pooling.

Figure 4. Indocyanine green angiography demonstrating both early and late hypofluorescence in the central macula of the right eye.

One day after presentation, BCVA was decreased to 20/100 in the right eye and remained 20/25 in the left. A trace relative afferent pupillary defect remained in the right eye but was less prominent than at presentation. Color vision was improved to 7/10 plates in the right eye and remained full in the left. Dilated funduscopy at this time revealed subtle macular whitening. Optical coherence tomography revealed focal subfoveal disruption of the outer retina, thickening at the level of the retinal pigment epithelium and trace subretinal fluid (Figure 1).

As she was seen after hours on the weekend, the patient returned the following day for further testing. Her vision remained unchanged at 20/100; however, the afferent pupillary defect had resolved and her color vision had returned to normal. Her funduscopic exam had become markedly abnormal with a grayish discoloration superior to the fovea (Figure 2). Fluorescein angiography demonstrated early patchy hyperfluorescence in the area of retinal changes with late pooling in the area of focal outer retinal disruption (Figure 3). Normal transit was observed in the left eye. Indocyanine green angiography revealed early hypofluorescence in the area of retinal changes in the right eye, which persisted in the late phases (Figure 4). Normal transit was again observed in the left eye. Repeat OCT demonstrated continued focal disruption of the inner segment/outer segment junction.

What is your diagnosis?

Focal disruption of outer retina

The differential diagnosis for focal disruption of the outer retina is broad and includes white dot syndromes such as multiple evanescent white dot syndrome and acute posterior multifocal placoid pigment epitheliopathy, solar retinopathy, laser injury, acute macular neuroretinopathy, central serous chorioretinopathy, unilateral acute idiopathic maculopathy, acute retinal pigment epitheliitis and idiopathic choroidal neovascularization.

On questioning, the patient denied sun gazing or exposure to lasers. There were no areas of focal leakage on fluorescein angiography suggestive of central serous chorioretinopathy. Furthermore, the fluorescein angiography findings of patchy early hypofluorescence and hyperfluorescence with two distinct areas of late hyperfluorescence (staining in the area of retinal pigment changes and pooling in the area of outer retina disruption) are characteristic in unilateral acute idiopathic maculopathy (UAIM) and have been well described. The fundus appearance was not classic for multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, acute retinal pigment epitheliitis or acute macular neuroretinopathy, nor would one expect the described appearance on fluorescein angiography in these diagnoses. Indocyanine green demonstrated both early and late hypofluorescence, excluding the possibility of a choroidal neovascularization. Based on the clinical appearance, early optic nerve findings and appearance on fluorescein angiography, we felt that UAIM was the most probable diagnosis in our patient.

Figure 5. One week after the onset of symptoms, pigment clumping was seen in the perifoveal region of the right eye.

Figure 6. Two weeks after the onset of symptoms, reorganization of the outer retina was seen on SD-OCT. Vision had improved to 20/30 at that time.

Discussion

UAIM was first described by Yannuzzi in 1991 as acute, unilateral severe vision loss with a central scotoma, usually seen in young adults after a flu-like illness. He described a shallow neurosensory detachment in the macula with associated white, gray or yellow thickening at the level of the retinal pigment epithelium. Some cases demonstrated vitreous cells, intraretinal hemorrhages or optic nerve findings. A few bilateral cases have been described. Fluorescein angiography findings of early hypofluorescence and hyperfluorescence with late pooling are characteristic. In general, vision spontaneously improves to 20/25 or better over the course of weeks. This spontaneous improvement is accompanied by resolution of the outer retinal disruption and late subretinal atrophic and pigmentary disturbances, often producing a “bull’s-eye” appearance in the macula. It has been hypothesized that UAIM represents an inflammatory process at the level of the retinal pigment epithelium and choroid, possibly associated with a viral etiology. In recent years, many cases in the literature have been linked to coxsackievirus infection, both clinically and with viral titers, prompting the suggestion that UAIM may be better termed “coxsackievirus maculopathy.”

On a subsequent follow-up visit, our patient’s parent volunteered that the flu-like illness that affected our patient’s siblings in the preceding weeks had been diagnosed as hand, foot and mouth disease by their pediatrician. Additionally, although she never felt unwell herself, our patient noted that she too had papular erythematous lesions on the palms of her hands 1 week before the onset of her visual symptoms, indicating probable coxsackievirus infection and reinforcing our diagnosis.

Clinical course

One week after presentation, pigment clumping was observed in the fundus of the right eye (Figure 5). Two weeks after the onset of symptoms, the patient’s vision had improved to 20/30 in the right eye. She reported near resolution of the scotoma, and OCT demonstrated significant reorganization of the outer retina (Figure 6). Her left eye remained unaffected throughout the clinical course.

References:
Beck AP, et al. Arch Ophthalmol. 2004;doi:10.1001/archopht.122.1.121.
Freund KB, et al. Arch Ophthalmol. 1996;doi:10.1001/archopht.1996.01100130547007.
Yannuzzi LA, et al. Arch Ophthalmol. 1991;doi:10.1001/archopht.1991.01080100091049.
For more information:
Kirstin L. Tawse, MD, and Nadia K. Waheed, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.
Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.

An 18-year-old woman presented to our clinic with a complaint of 3 days of decreased vision in her right eye. She reported that the vision in her right eye had appeared “washed out” for 2 days, followed by the development of a dark spot in her central vision. She described mild irritation of the right eye but denied any eye pain, pain with eye movement, redness, photophobia, photopsias or ocular trauma. She reported that her younger siblings had a flu-like illness several weeks before the onset of her symptoms but that she herself had not been ill. Her ocular history included only myopia. She had no medical history. She was on no medications.

Examination

At the time of presentation, best corrected visual acuity was 20/80 in the right eye and 20/25 in the left eye. IOP was within normal limits. Pupils were round and reactive to light in both eyes with a 1+ relative afferent pupillary defect noted in the right eye. On Ishihara color plate testing, the patient correctly identified only the control plate with the right eye and 10/10 plates with the left eye. Slit lamp exam was unremarkable, and dilated funduscopy demonstrated normal-appearing fundi in both eyes. Both optic nerves were found to have 0.1 cup-to-disc ratio with no edema. Humphrey visual field testing revealed a small paracentral scotoma in the right eye, which was also seen on Amsler grid testing. The visual field was full in the left eye.

Given the acute onset, normal-appearing fundus, afferent pupillary defect and decreased color vision, concern was initially for a primary process of the optic nerve, with a suspicion for retrobulbar optic neuritis. An MRI of the orbits was obtained and demonstrated right optic nerve hyperintensity without enhancement as well as a right carotid artery flow void, possibly representing a dissection, thrombosis or congenital variant. Although a carotid dissection would be unlikely to result in an isolated ipsilateral optic neuropathy, the patient underwent urgent MRA of the head and neck to exclude emergent diagnoses. The MRA revealed congenital hypoplasia of the right internal carotid, a normal variant and incidental finding.

Figure 1. Spectral-domain OCT of the macula of the right eye showing disruption and effacement of the outer retina at the level of the inner segment/outer segment, thickening at the level of the retinal pigment epithelium and trace subretinal fluid (a). Normal foveal contour and retinal architecture was seen in the left eye (b).

Images: Tawse KL, Waheed NK

Figure 2. Fundus photography of the right eye showing a deep yellowish discoloration superior to the fovea in the right eye. A normal fundus was observed in the left eye.

Figure 3. Early patchy hypofluorescence and hyperfluorescence were seen superior to the fovea on fluorescein angiography in the right eye with late patchy staining in the same area and central pooling.

Figure 4. Indocyanine green angiography demonstrating both early and late hypofluorescence in the central macula of the right eye.

One day after presentation, BCVA was decreased to 20/100 in the right eye and remained 20/25 in the left. A trace relative afferent pupillary defect remained in the right eye but was less prominent than at presentation. Color vision was improved to 7/10 plates in the right eye and remained full in the left. Dilated funduscopy at this time revealed subtle macular whitening. Optical coherence tomography revealed focal subfoveal disruption of the outer retina, thickening at the level of the retinal pigment epithelium and trace subretinal fluid (Figure 1).

As she was seen after hours on the weekend, the patient returned the following day for further testing. Her vision remained unchanged at 20/100; however, the afferent pupillary defect had resolved and her color vision had returned to normal. Her funduscopic exam had become markedly abnormal with a grayish discoloration superior to the fovea (Figure 2). Fluorescein angiography demonstrated early patchy hyperfluorescence in the area of retinal changes with late pooling in the area of focal outer retinal disruption (Figure 3). Normal transit was observed in the left eye. Indocyanine green angiography revealed early hypofluorescence in the area of retinal changes in the right eye, which persisted in the late phases (Figure 4). Normal transit was again observed in the left eye. Repeat OCT demonstrated continued focal disruption of the inner segment/outer segment junction.

What is your diagnosis?

PAGE BREAK

Focal disruption of outer retina

The differential diagnosis for focal disruption of the outer retina is broad and includes white dot syndromes such as multiple evanescent white dot syndrome and acute posterior multifocal placoid pigment epitheliopathy, solar retinopathy, laser injury, acute macular neuroretinopathy, central serous chorioretinopathy, unilateral acute idiopathic maculopathy, acute retinal pigment epitheliitis and idiopathic choroidal neovascularization.

On questioning, the patient denied sun gazing or exposure to lasers. There were no areas of focal leakage on fluorescein angiography suggestive of central serous chorioretinopathy. Furthermore, the fluorescein angiography findings of patchy early hypofluorescence and hyperfluorescence with two distinct areas of late hyperfluorescence (staining in the area of retinal pigment changes and pooling in the area of outer retina disruption) are characteristic in unilateral acute idiopathic maculopathy (UAIM) and have been well described. The fundus appearance was not classic for multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, acute retinal pigment epitheliitis or acute macular neuroretinopathy, nor would one expect the described appearance on fluorescein angiography in these diagnoses. Indocyanine green demonstrated both early and late hypofluorescence, excluding the possibility of a choroidal neovascularization. Based on the clinical appearance, early optic nerve findings and appearance on fluorescein angiography, we felt that UAIM was the most probable diagnosis in our patient.

Figure 5. One week after the onset of symptoms, pigment clumping was seen in the perifoveal region of the right eye.

Figure 6. Two weeks after the onset of symptoms, reorganization of the outer retina was seen on SD-OCT. Vision had improved to 20/30 at that time.

Discussion

UAIM was first described by Yannuzzi in 1991 as acute, unilateral severe vision loss with a central scotoma, usually seen in young adults after a flu-like illness. He described a shallow neurosensory detachment in the macula with associated white, gray or yellow thickening at the level of the retinal pigment epithelium. Some cases demonstrated vitreous cells, intraretinal hemorrhages or optic nerve findings. A few bilateral cases have been described. Fluorescein angiography findings of early hypofluorescence and hyperfluorescence with late pooling are characteristic. In general, vision spontaneously improves to 20/25 or better over the course of weeks. This spontaneous improvement is accompanied by resolution of the outer retinal disruption and late subretinal atrophic and pigmentary disturbances, often producing a “bull’s-eye” appearance in the macula. It has been hypothesized that UAIM represents an inflammatory process at the level of the retinal pigment epithelium and choroid, possibly associated with a viral etiology. In recent years, many cases in the literature have been linked to coxsackievirus infection, both clinically and with viral titers, prompting the suggestion that UAIM may be better termed “coxsackievirus maculopathy.”

On a subsequent follow-up visit, our patient’s parent volunteered that the flu-like illness that affected our patient’s siblings in the preceding weeks had been diagnosed as hand, foot and mouth disease by their pediatrician. Additionally, although she never felt unwell herself, our patient noted that she too had papular erythematous lesions on the palms of her hands 1 week before the onset of her visual symptoms, indicating probable coxsackievirus infection and reinforcing our diagnosis.

Clinical course

One week after presentation, pigment clumping was observed in the fundus of the right eye (Figure 5). Two weeks after the onset of symptoms, the patient’s vision had improved to 20/30 in the right eye. She reported near resolution of the scotoma, and OCT demonstrated significant reorganization of the outer retina (Figure 6). Her left eye remained unaffected throughout the clinical course.

References:
Beck AP, et al. Arch Ophthalmol. 2004;doi:10.1001/archopht.122.1.121.
Freund KB, et al. Arch Ophthalmol. 1996;doi:10.1001/archopht.1996.01100130547007.
Yannuzzi LA, et al. Arch Ophthalmol. 1991;doi:10.1001/archopht.1991.01080100091049.
For more information:
Kirstin L. Tawse, MD, and Nadia K. Waheed, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.
Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.