Astrocytic Hamartoma – April 2018

April 2018

13-year-old boy was referred to Illinois Retina Associates for suspicion for a choroidal nevus. He had no complaints.

Past Medical History

He had a history of hypertension due to underlying polycystic kidney disease.

Medications

He was on medications for hypertension

Ocular Examination

  • Vision was 20/25 both eyes
  • Pressures were 10 and 12
  • Pupils were equal and reactive without relative afferent pupillary defect
  • The anterior segments were unremarkable
  • The posterior segment photos are shown below (Figure 1). No additional pathology was seen in either periphery
Posterior Segment Photographs
Figure 1: Posterior segment photographs

Differential Diagnosis

  • Astrocytic Harmartoma
  • Retinoblastoma
  • Myelinated Nerve Fiber Layer
  • Amelanotic Melanoma
  • Choroidal Neovascularization

Further Workup

Upon questioning, the young man endorsed that he did have 6 unusual patches on his skin, which were confirmed to be consistent with ash-leaf spots.

Diagnosis:

Astrocytic hamartoma of the retina due to underlying tuberous sclerosis.

Discussion

Tuberous sclerosis is a systemic disorder that can result in non-cancerous lesions in multiple organ systems. Over 90% of affected patients will have skin lesions, neurological symptoms and kidney problems. This autosomal dominant condition is believed to affect 1 in 6,000 people. The diagnosis is made based on the patient having to major, or one major and two minor features (listed below).

Major Features

  • Facial angiofibromas or forehead plaque pits in dental enamel
  • Non-traumatic ungula or periungual fibroma
  • Hypomelanotic macules (three or more)
  • Shagreen patch (connective tissue nevus) migration lines
  • Multiple retinal nodular hamartomas
  • Cortical tuber
  • Subependymal nodule
  • Cardiac rhabdomyoma, single or multiple
  • Lymphangiomyomatosis, renal angiomyolipoma, or both

Minor Features

  • Multiple, randomly distributed
  • Hamartomatous rectal polyps
  • Bone cysts
  • Cerebral white matter radial
  • Gingival fibromas
  • Non-renal hamartoma
  • Retinal achromic patch
  • Confetti-like skin lesions
  • Multiple renal cysts

Approximately 45% of patients with tuberous sclerosis have retinal astrocytic hamartomas. Most will maintain a stable size and will not cause visual problems. However, a minority may have a symptomatic increase in lesion size, which may be slowed or reversed with oral sirolimus. Even without an increase in size, some astrocytic hamartomas are associated with retinal bleeding or edema which may be responsive to anti-VEGF intravitreal injections.

References

Curatolo, P., R. Bombardieri, and S. Jozwiak. “Tuberous Sclerosis.” Lancet (London, England) 372.9639 (2008): 657-68. Print.

Lonngi, M., A. S. Gold, and T. G. Murray. “Combined Bevacizumab and Triamcinolone Acetonide Injections for Macular Edema in a Patient with Astrocytic Hamartomas and Tuberous Sclerosis.” Ophthalmic surgery, lasers & imaging retina 44.1 (2013): 85-90. Print.

Shepherd, C. W., et al. “Tuberous Sclerosis Complex in Olmsted County, Minnesota, 1950-1989.” Archives of Neurology 48.4 (1991): 400-1. Print.

Zhang, Z. Q., et al. “Sirolimus for Retinal Astrocytic Hamartoma Associated with Tuberous Sclerosis Complex.” Ophthalmology 122.9 (2015): 1947-9. Print.

Pseudoxanthoma Elasticum – March 2018

March 2018

23-yearold Caucasian female presented to Illinois Retina Associates reporting a large blind spot with resulting poor vision in her right eye since 2016. She had been previously treated with a series of intravitreal injections in the affected eye at a California retina practice. Her left eye is unaffected.

Past Medical History

Otherwise healthy, non-contributory

Ocular Examination

Visual acuity is count fingers at 1 ft. in the right eye and 20/20 in the left. IOP is normal in both eyes. Slit lamp examination for the anterior segment is normal bilaterally. Fundus examination is as shown below and is notable for extensive subretinal fibrosis in the right eye as well as angiod streaks emanating from the optic disc in the left eye. There are also characteristic pigment changes temporal to the macula in both posterior poles (Figures 1 & 2).


Figure 1

Figure 2

Differential Diagnosis

  • Pseudoxanthoma Elasticum
  • Paget’s Disease
  • Sickle Cell, Thalassemia, or other Hemoglobinopathies
  • Ehlers-Danlos Syndrome
  • Lacquer Cracks (Pathologic Myopia)
  • Presumed Ocular Histoplasmosis

Additional Testing

OCT shows extensive subretinal fibrosis with overlying subretinal fluid in the right eye. OCT of the left eye is grossly normal (Figure 3).

Subretinal Bleed
Figure 3

Fluorescein angiogram of the right eye shows extensive late hyperfluorescence consistent with staining of the above-mentioned subretinal fibrosis. There is early hyperfluorescence suggestive of window defect corresponding to the angioid streaks in the left eye fundus (Figures 4 ∓ 5).


Figure 4

Figure 5

External Examination of the patient’s head and neck revealed a patch of skin with irregular contour was noted on the back of her neck (Figure 6).


Figure 6

Additionally, genetic testing obtained showed that the patient was both ABCC6 and ENPP1 positive.

Diagnosis:

Pseudoxanthoma Elasticum.

With the presence of angioid streaks emanating from the bilateral optic discs, along with the characteristic RPE changes in the posterior pole and pathognomonic skin findings on the patient’s neck, the patient’s presentation is highly suggestive of pseudoxanthoma elasticum. The extensive subretinal fibrosis and history of prior anti-VEGF injections is indicative of previous secondary choroidal neovascularization in the right eye.

Discussion

Pseudoxanthoma elasticum is an inherited disorder, which is associated with accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Bruch’s membrane in the eye. Characteristic lesions of the posterior pole include angioid streaks, peau d’orange fundus, and choroidal neovascularization. Commonly seen skin lesions are ivory-colored papules in a reticular pattern that are most often noted on the neck and large flexor surfaces. People with this condition also frequently exhibit cardiovascular complications.

The disease follows an autosomal recessive inheritance pattern. Recently the ABCC6 gene, which encodes a transmembrane transport protein, was implicated in causing this condition. Mutation of this gene causes an accumulation of extracelluar material

There is no treatment for the underlying condition, but therapies are generally intended to minimize secondary complications of the disease. Angioid streaks, or breaks in the thickened, calcific Bruch’s membrane eventually allow inward growth of fibrovascular tissue and choroidal neovascularization. End-stages of the disease generally include extensive subretinal fibrosis and disciform scarring, leading to profound visual impairment. Early treatment with anti-VEGF targeting CNV is aimed at preventing scarring, and thus significant visual loss.

References

Finger, R. P., Issa, P. C., Ladewig, M. S., Götting, C., Szliska, C., Scholl, H. P., & Holz, F. G. (2009). Pseudoxanthoma elasticum: genetics, clinical manifestations and therapeutic approaches. Survey of ophthalmology, 54(2), 272-285.

Submacular Bleed – February 2018

February 2018

A 71 year old woman was referred to Illinois Retina Associates after noticing a black film over her vision in her left eye for 4 days. There was no pain and over that time the vision has not been getting better or worse. There was no inciting incident.

Past Medical History

Insulin dependent diabetes, hypertension, congestive heart failure, renal insufficiency

Ocular Examination

Vision was 20/30 in the right eye and hand motion in the left eye. Pressures were 9mmHg in the right eye and 14mmHg in the left eye. The anterior segments were remarkable only for moderate cataracts which were symmetric. The right fundus was remarkable only for mild pigment changes (Figure 1). The left eye showed a large amount of subretinal blood involving the majority of the macula and extending into the superior retina (Figure 2).

Subretinal Bleed
Figure 1
Subretinal Bleed
Figure 2

Differential Diagnosis

  • Exudative age related macular degeneration
  • Diabetic eye disease
  • Retinal macroaneurysm
  • Polypoidal choroidal vasculopathy
  • Hypertensive retinopathy
  • Choroidal neovascularization due to other cause
    • Myopia
    • Ocular histoplasmosis syndrome
    • Psueoxanthoma elasticum
    • Peripapillary atrophy
    • Laquer crack
    • Choroidal rupture

Additional Testing

OCT in the right eye showed mild drusen and RPE changes. The left eye showed a large amount of thick subretinal hemorrhage (Figure 3).

Subretinal Bleed
Figure 3

FA was confirmed drusen in the right eye and was notable for extensive blocking consistent with subretinal hemorrhage in the left eye (Figure 4).

Subretinal Bleed
Figure 4

Diagnosis:

The patient was diagnosed with a large submacular bleed, most likely due to polypoidal choroidal vasculopathy. The risks and benefits of surgical displacement of the blood vs treatment with anti-VEGFs were discussed. The patient elected to proceed with a vitrectomy, subretinal tissue plasminogen activator injection and air bubble placement to displace the large amount of submacular blood.

Follow up

The patient did well after surgery. She received a series of anti-VEGF injections to treat the underlying bleed. Her best corrected vision recovered from hand motion to 20/50. The macular blood resolved as shown in Figure 5, although some subretinal fibrosis remains superiorly.

Subretinal Bleed
Figure 5

Discussion

Although the mainstay for the treatment of subretinal bleed is treatment of the underlying cause, usually with anti-VEGF injections, there are a limited number of cases where displacement of a thick layer of submacular blood can be a useful adjunct for visual recovery. There are no strict criteria but subretinal blood that is at least twice as thick as the retina may be considered for displacement. A series of 100 of these surgeries had an 80% success rate at displacing the blood and found that post operative anti-VEGF helped patients achieve maximum visual potential.

References

Chang, Garg, et al. “Management of Thick Submacular Hemorrhage With Subretinal Tissue Plasminogen Activator and Pneumatic Displacement for Age-Related Macular Degeneration.” american Journal of Ophthalmology. Vol 157:6 pages 1250-1257; 2014

Choroidal Rupture – January 2018

January 2018

48 year-old male patient referred to Illinois Retina Associates for evaluation one month following blunt ocular trauma, inflicted when a bungee cord released suddenly and struck him in the left eye and left side of the face. The patient noted sudden, profound reduction of vision immediately following the incident, which seems to have gradually improved. He also noticed a large red floater following the incident, which has since become smaller and moved more inferior in his field of view.

The patient is otherwise healthy with no significant past medical history or past ocular history.

Upon examination, visual acuity was 20/15 and 20/25+1 in the right and left eyes, respectively. Intraocular pressure was 20 bilaterally. Anterior segment examination was unremarkable in both eyes. Posterior segment examination was notable for trace pigmented cell in the anterior vitreous, mild chronic vitreous hemorrhage settling inferiorly, and a vertically oriented curvilinear hypopigmented lesion within the macula. The posterior segment examination of the right eye was normal. (Figure 1)

Parry Romberg Syndrome
Figure 1

Differential Diagnosis

  • Choroidal Rupture
  • Laquer Cracks
  • Angioid Streaks

OCT was performed, which demonstrated an RPE disruption with a small foci of overlying subretinal hyperreflective material, but an absence of subretinal fluid, in the nasal left macula. Macula OCT of the right eye was unremarkable (Figures 2 & 3).

Parry Romberg Syndrome
Figure 2
Parry Romberg Syndrome
Figure 3

Fluorescein angiography of the left eye showed a normal transit, but an early hyperfluorescence of the lesion mentioned, consistent with window defect. Transit of the right eye revealed late leakage at the superior aspect of the lesion, suggestive of macular edema, likely secondary to choroidal neovascularization (Figure 4).

Parry Romberg Syndrome
Figure 4

Diagnosis:

A well-defined hypopigmented streak with an RPE and Bruch’s membrane disruption noted on OCT, as well as concurrent window defect and an associated focus of late leakage on FA, is strongly suggestive of choroidal rupture with secondary choroidal neovascularization, particularly in the context of new symptoms immediately following trauma.

Discussion

Choroidal rupture is a relatively commonly occurring entity in blunt ocular trauma. Rupture can be a direct result of traumatic forces, occurring at the site of impact, or an indirect effect, secondary to forces transferred through the vitreous or walls of the globe.1,3 The latter is more common. Most frequently, the rupture occurs temporal to the disc, often times within the macula.

The classic curvilinear hypopigmented fundus lesion attributed to choroidal rupture represents a disruption of both Bruch’s membrane and the overlying RPE. This can be associated with subretinal hemorrhage and subsequent choroidal neovascularization, as in this case, but most often vision loss immediately following the injury can be attributed to concurrent vitreous hemorrhage, in which case vision improves gradually as the hemorrhage clears. Final visual prognosis depends on the location of the rupture relative to the fovea, as well as the presence of sequelae such as choroidal neovascularization and subretinal scarring.

There is no treatment at this time for the choroidal rupture itself. However, development of choroidal neovascularization as a result of the rupture can be addressed effectively with anti-VEGF agents, or in some cases photodynamic therapy. Previously, submacular sugery was undertaken for large choroidal neovascular membranes with significant visual impact, but this has fallen largely out of favor since the advent of anti-VEGF injections due to their dramatic efficacy and relatively minimal potential for adverse effects.

References

1. Ament, C. S., Zacks, D. N., Lane, A. M., Krzystolik, M., D’Amico, D. J., Mukai, S., … & Miller, J. W. (2006). Predictors of visual outcome and choroidal neovascular membrane formation after traumatic choroidal rupture. Archives of ophthalmology, 124(7), 957-966.

2. Gross, J. G., King, L. P., de Juan, E., & Powers, T. (1996). Subfoveal neovascular membrane removal in patients with traumatic choroidal rupture. Ophthalmology, 103(4), 579-585.

3. Wood, C. M., & Richardson, J. (1990). Indirect choroidal ruptures: aetiological factors, patterns of ocular damage, and final visual outcome. British journal of ophthalmology, 74(4), 208-211.

Parry Romberg Syndrome – December 2017

December 2017

History of Present Illness: The patient was a healthy 17 year old who had been noticing a blurred vision in his right eye. It started with floaters 3 months prior to presentation. He was seen locally before being referred to Illinois Retina Associates.

Past Medical History: None.

Ocular Exam: Vision was 20/40 in the right eye and 20/20 in the left. Intraocular pressures were normal in both eyes. The anterior segments were unremarkable including an absence of cells. There were 1+ vitreal cells in the right eye and none in the left. The right eye macula (Figure 1) and posterior pole (Figure 2) are shown below. The left posterior exam was unremarkable.

Parry Romberg Syndrome
Figure 1
Parry Romberg Syndrome
Figure 2

Differential Diagnosis

  • Varicella Zoster
  • Herpes Simplex
  • Susac Syndrome
  • Eale’s Disease
  • Lyme Disease
  • West Nile
  • Sarcoid
  • Syphilis
  • TB
  • Other syndrome associated with vasculitis

Further Testing

FA showed increase vascularity over the disc and capillary dropout inferonasally in the right eye.

Parry Romberg Syndrome
Figure 3
Parry Romberg Syndrome
Figure 4

Blood testing:
Abnormal: FTA+, RPR negative, VZV IgG+, IgM-, Coxsackie B5+

Normal or negative: CBC, ESR, ANA, ANCAs, B51, toxo, Lyme, bartonella, quant gold, HIV, West Nile, blood cx, CXR, HSV CMC

MRI:

Parry Romberg Syndrome
Figure 5
Parry Romberg Syndrome
Figure 6

Follow Up

The patient was started on oral methotrexate and his vision and exam improved.

Diagnosis:

Parry Romberg Syndrome is a rare condition characterized by progressive atrophy of one side of the head and face.The most common sign is subcutaneous atrophy, which is especially striking later in the disease course, but other structures, including the brain and eye, may be affected. The most common ocular manifestation is enophtalmos followed by eyelid dysfunction related to the facial atrophy. Retinal vasculitis related to Parry Romberg has been reported but is quite rare. Immunosuppression has bee shown to be helpful in some of these cases.

References

Bellusci C, Liguori R, Pazzaglia A, Badiali L, Schiavi C, Campos EC. Bilateral Parry-Romberg syndrome associated with retinal vasculitis. Eur J Ophthalmol. 2003

Bucher F, Fricke J, Neugebauer A, Cursiefen C, Heindl LM. Ophthalmological manifestations of Parry-Romberg syndrome. Surv Ophthalmol 2016; 61:693-701.

Yildirim O, Dinc E, Oz O. Parry-Romberg syndrome associated with anterior uveitis and retinal vasculitis. Can J Ophthalmol. 2010;45(3):289e90

Birdshot Chorioretinopathy – November 2017

November 2017

HPI: A 47-year old Caucasian female is referred to Illinois Retina Associates for evaluation of floaters. She reports worsening floaters in both eyes for three months, as well as occasional flashing lights in both eyes. She denies any eye pain.

POH/PMH: She has no prior history of eye problems. The patient has a history of hypothyroidism for which she takes Synthroid.

Exam: the patient’s visual acuity is 20/25 and 20/20 in the right and left eyes, respectively. Intraocular pressures are 15 and 16. Pupil, motility, and confrontational field examination were within normal limits. Slit lamp examination showed a normal ocular surface, anterior chamber, and lens bilaterally with no sign of anterior chamber cell or flare.

Posterior segment examination demonstrated trace cell in the anterior vitreous and vitreous syneresis bilaterally. Optic discs were normal in appearance. The retinal vasculature in the right eye appeared normal, however, in the left eye there was mild venous sheathing and tortuosity. On careful examination there were also small, round, yellow lesions deep to the peripheral retina in both eyes.

Birdshot Chorioretinopathy
Figure 1
Birdshot Chorioretinopathy
Figure 2

Differential Diagnosis

  • Multifocal Choroiditis and Panueveitis
  • Carcoidosis
  • Intermediate Uveitis (Pars Planitis)
  • Infectious (Syphilis, TB, Lyme, Whipple’s Disease, Presumed Ocular Histoplasmosis)
  • Lymphoma
  • Birdshot Chorioretinoptahy
  • Other White Dot Syndromes (i.e. PIC, MEWDS, etc)
  • Sympathetic Ophthalmia
  • Endogenous Endophthalmitis

OCT is within normal limits on both eyes.

Further Testing

Birdshot Chorioretinopathy
Figure 3

Fluorescein angiogram demonstrated late vascular leakage around larger vessels diffusely in both eyes, suggestive of a retinal vasculitis.

Birdshot Chorioretinopathy
Figure 4
Birdshot Chorioretinopathy
Figure 5

Humphrey visual field testing (24-2) revealed superior arcuate defects in both eyes.

Additionally, Iridocyanine Green was performed which showed hypofluorescence of the scattered peripheral lesions in both eyes in early and late frames.

The following laboratory workup was ordered:

ESR, CBC, ACE, Lysozyme, Quantiferon, ANCA, Rheumatoid Factor, Lyme, FTA-ABS, and HLA A29, all of which were normal except the HLA A29 was positive. Chest x-ray was also normal.

On further testing, ERG showed mildly abnormal scotopic B wave amplitudes of 187 and 143, and 30Hz flicker latency was 30.5 and 32 in the right and left eyes, respectively.

Diagnosis:

A diagnosis of Birdshot Chorioretinopathy was made based on the characteristic fundus appearance with scattered yellow “birdshot spots” throughout the mid-peripheral retina, along with positive HLA A29 testing, presence of vitritis, and ICG showing typical hypofluorescence of the above mentioned lesions. A reasonable suspicion for masquerade syndrome must be maintained until response to treatment is observed, since malignancy cannot be initially ruled out without a vitreous biopsy.

Discussion

Birdshot Chorioretinopathy is one of the inflammatory chorioretinopathies termed, “White Dot Syndromes,” which are loosely related entities grouped together based on similarities in clinical appearance. They generally present with some degree of multiple yellow-white lesions affecting various layers of the choroid, RPE, and/or retina.

Specifically, birdshot chorioretinopathy presents uniformly with vitritis, and anterior chamber inflammation is usually absent or minimal. There are yellowish lesions at the level of the deep retina scattered throughout the mid-peripheral retina, usually sparing the macula and posterior pole. Fluorescein angiography most often shows varying degrees of vasculitis, but can also show leakage suggestive with cystoid macular edema. Iridocyanine Green angiography will reveal persistent hypofluorescence of the yellow fundus lesions. ERG testing is also useful for both initial diagnosis and monitoring the long-term progression of the disease. Greater than 90% of patients with birdshot are HLA-A29 positive on blood testing, so a positive HLA typing is very supportive of the diagnosis, however it is not necessary for the diagnosis to be made.

Birdshot chorioretinopathy affects women more than men, usually in their fourth to sixth decade of life. Presenting symptoms include nyctalopia, floaters, photopsias, scotomas, and decreased vision. Visual acuity is relatively preserved, however patients often complain of symptoms that seem out of proportion to measured acuity. Most patients have a recurrent course involving multiple exacerbations and remissions. When loss of retinal function occurs it is diffuse, and it is attributed to chronic hypoperfusion and changes in the RPE and choroid. Central vision loss can occur from cystoid macular edema and optic nerve atrophy.

Treatment for birdshot chorioretinopathy typically involves an initial course of topical and oral corticosteroids. Localized therapies include intravitreal steroid implants for sustained control of the disease and sub-Tenon’s steroid injections for macular edema. Eventually, it is desirable for patients to transition to long-term treatment on steroid-sparing agents, such as methotrexate, or biologics, such as infliximab.

References

Artornsombudh, P., Gevorgyan, O., Payal, A., Siddique, S. S., & Foster, C. S. (2013). Infliximab treatment of patients with birdshot retinochoroidopathy. Ophthalmology, 120(3), 588-592.

Rothova, A., Berendschot, T. T., Probst, K., van Kooij, B., & Baarsma, G. S. (2004). Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology, 111(5), 954-959.

Crawford, C. M., & Igboeli, O. (2013). A review of the inflammatory chorioretinopathies: the white dot syndromes. ISRN inflammation, 2013.

Polypoidal Choroidal Vasculopathy – October 2017

October 2017

HPI: A 52 year old man referred to Illinois Retina Associates for blurred vision in the right eye. The blur has been worsening in the central vision over the preceding 2 months. There were no symptoms in the other eye.

Past medical history: The patient was healthy and not on any medications.

Ocular Examination: Vision was 20/200 in the right eye and 20/25 in the left ye. Pressures were normal. There were mild cataracts in both eyes. The posterior exam was notable for subretinal hemorrhage in inferiorly in the right eye (figure 1) and a solitary CHRPE in the left eye.

Abnormal Retinal Appearance
Figure 1

Differential Diagnosis

  • Age related macular degeneration
  • Choroidal neovascularization due to:
    • Pseudoxanthoma elasticum
    • Peripapillary atrophy
    • Laquer crack
    • Choroidal rupture
  • Polypoidal choroidal vasculopathy
  • Peripheral exudative hemorrhagic chorioretinopathy
  • Retinal artery macroaneurysm

Further Testing

OCT: The right eye showed hyper-reflective subretinal material inferiorly. The left eye showed pigment epithelial detachments.

Abnormal Retinal Appearance
Figure 2
Abnormal Retinal Appearance
Figure 3
Abnormal Retinal Appearance
Figure 4
Abnormal Retinal Appearance
Figure 5

FA and ICG Right eye showed polypoidal changes in the ICG without leakage on the FA. The left eye was unremarkable.

Abnormal Retinal Appearance
Figure 6

OCT angiography right eye also shows the thickened vessel in the choroid.

Abnormal Retinal Appearance
Figure 7

Diagnosis:

Given the thickened vessel in the choroid characteristic of a polyp and the lack of findings consistent with choroidal neovascularization on FA, the diagnosis of Polypoidal Choroidal Vasculopathy was made.

Follow Up

The patient was treated with intravitreal bevacizumab and his vision improved to 20/50 from 20/200 in the right eye.

Discussion

Polypoidal choroidal vasculopathy is an exudative macular disease that shares some characteristics with age-related macular degeneration. Both are causes of fluid and bleeding in the macula that increase in frequency with increasing age. While age-related macular degeneration is most common in Caucasians, polypoidal choroidal vasculoptahy is more commonly seen in those of Asian, Hispanic or African descent. The underlying cause is an abnormality in the choroidal circulation that results in a dilated choroidal vessel, known as a polyp. Because these vessels are primarily seen only with ICG, this condition is likely frequently underdiagnosed.

Treatment is similar to that of exudative age-related macular degeneration. These patients often have an improvement in fluid and vision with intravitreal anti-VEGF (Vascular endothelial growth factor) agents.

References

Ryan Retina, Chapter 71, Polypoidal Choroidal Vasculopathy, Xiaoxin Li OIntravitreal injection of aflibercept in patients with polypoidal choroidal. Maruyama-Inoue M, Sato S, Yamane S, and KAdonosono K. Retina 2017.

Susac’s Syndrome – September 2017

September 2017

HPI: A 37-year-old Caucasian female presents, urgently referred from a community eye care provider, complaining of progressive peripheral visual loss as well as fluctuating numbness and tingling, spreading to all four extremities. Upon further questioning, she also reports intermittently diminished hearing.

Past medical history is remarkable only for long-standing hypothryoidism, treated with supplementation. Past ocular history is non-contributory.

Examination: Uncorrected visual acuity was 20/25 and 20/20 in the right and left eyes, respectively. Intraocular pressure was normal in both. Ocular motility, confrontational field, and pupillary examination were unremarkable, showing no relative afferent pupillary defect. Slit lamp examination of the anterior chamber was also normal, including no anterior chamber inflammation, with a clear cornea and lens in each eye.

On fundus examination, the patient was noted to have healthy appearing nerves in both eyes. Peripheral retinal examination of the right eye was notable for faint whitening in the distribution of a peripheral branch of the superonasal arcade arteriole. Similarly, examination of the left eye demonstrated whitening and numerous cotton-wool spots along the proximal inferotemporal arcade vessels and within the inferotemporal macula. These findings are suggestive of branch retinal artery occlusions of both eyes (Figure 1 & 2)

Abnormal Retinal Appearance
Figure 1
Posterior Segment Exam
Figure 2

Differential Diagnosis for occlusive retinal vasculitis

  • Infection (i.e. syphilis, tuberculosis, Lyme disease, Whipple’s deisease)
  • Embolic phenomenon
  • Hypercoagulable states (i.e. antiphospholipid antibodies, prothrombin mutation, antithrombin deficiency, protein C and S deficiencies)
  • Susac’s Syndrome
  • Systemic lupus erythematosus
  • Behcet’s syndrome
  • Polyarteritis nodosa
  • Sarcoidosis
  • Multiple Sclerosis
  • Granulomatosis with polyangitis

Further Testing

Optical coherence tomography of the involved areas showed inner retinal thickening with significant nerve fiber layer swelling, also consistent with retinal arterial ischemia (Figure 3).

Abnormal Retinal Appearance
Figure 3

Fluorescein angiography of both eyes demonstrated focal late staining of the corresponding arterioles with either significantly delayed or absent filling distal to the lesions in the superonasal and inferotemproral arcade vessels in the right and left eyes, respectively (Figures 4 & 5).

Abnormal Retinal Appearance
Figure 4
Posterior Segment Exam
Figure 5

MRI with and without contrast of the brain demonstrated multiple hyperintense foci within the corpus callosum on FLAIR imaging, as well as generalized leptomeningeal enhancement and scattered punctate foci of cortical diffusion restriction (Figure 6).

Posterior Segment Exam
Figure 6

Laboratory testing, including infectious, general inflammatory and vasculitis-specific workup were subsequently negative.

Diagnosis

– A young, otherwise healthy female presenting with bilateral acute occlusive retinal arteritis in conjunction with neurological symptoms, particularly hearing loss is strongly suggestive of Susac’s Syndrome. MRI findings of multiple hyperintense foci within the body of the corpus callosum are virtually pathognomonic for this condition. This, in conjunction with the negative serum testing for other infectious and inflammatory etiologies, provided sufficient basis for the diagnosis of Susac’s Syndrome.

The patient was last seen 3 months after initial presentation with stable visual symptoms, intact central vision and improving neurological symptoms. Hearing remains impaired in one ear. Her treatment consists of a slow oral steroid taper, intravenous IgG twice monthly, and oral Cellcept.

Discussion

Susac’s Syndrome, also known as retinocochleocerebral vasculopathy, classically consists of a triad of encephalopathy, branch retinal artery occlusions, and hearing loss. It is an autoimmune endotheliopathy, suggesting that it is caused by autoantibodies directed against the endothelial cells of the arterioles. One or more of the “triad” symptoms may not be present or may fail to be recognized on initial presentation. Often, the encephalopathic component is accompanied or preceeded by migraine headaches. Typically, this condition is seen in young women, between 20 and 40 years of age, however it can be observed in other subsets of the population.

As mentioned above, pathognomonic of Susac’s are findings of hyperintense foci within the corpus callosum on FLAIR MRI imaging, best seen in sagittal cuts, which represent small acute infarcts. Because of their appearance they are often referred to as “snowballs” or a “string of pearls”. Later, these fade to become hypointense, particularly on T1 imaging, and they are then referred to as central callosal “holes”.

It is essential that Susac’s syndrome be diagnosed promptly, since if treatment is delayed it can ultimately lead to permanent disability or death. Once diagnosed, treatment consists of high-dose corticosteroids, coupled with an immunosuppressant such as Cellcept, Intravenous IgG is also helpful to gain control of the disease.

References

Magro, c.M., Poe, J.C., Lubow, M. & Susac, J.O. (2011). Susac Syndrome: An Organ-Specific Autoimmune Endotheliopaty Syndrome Associated With Anti-Endothelial Cell Antibodies. American Journal of clinical pathology, 136(6), 903-912.

Rennebohm, R., Susa, J.O., Egan, R.A., & Daroff, R.B. (2010). Susac’s syndrome – update. Journal of the neurological sciences299(1), 86-91

Rennebohm, R.M., & Susac, J.O. (2007). Treatment of Susac’s Syndrome. Journal of the neurological sciences 257(1), 215-220

Susa, J.O., Murtagh, F.R., Egan, R.A., Berger, J.R., Bakshi, R., Lincoff, N., & Lee, A.G.(2003). MRI Findings in Susac’s Syndrome Neurology 61(12), 1783-1787

Retinochorioidal Coloboma – August 2017

August 2017

HPI: A 28 year old man was referred to Illinois Retina Associates for blurred vision in his right and left eyes. The right eye was more severely affected.

PMH:Mild Asthma.

Ocular Examination: Vision was 20/20 in both eyes without correction. Intraocular pressures were normal in both eyes. Pupils were equal round and reactive. The eyelids and anterior segments were unremarkable. The right eeye was notable for an optic nerve pit and the right periphery showed 2 inferior areas of abnormal retinal appearance (Figure 1). the left eye had an unremarkable posterior segment exam (Figure 2).

Abnormal Retinal Appearance
Figure 1
Posterior Segment Exam
Figure 2

Differential Diagnosis

  • Congenital Optic Pit
  • Coloboma
  • Combined Coloboma and Optic Pit
  • Glaucoma
  • Staphyloma due to High Myopia
  • Atrophy due to Retinal Insult
  • Systemic Syndromes: CHARGE, Mackel-Gruber, Goltz, Aicardi, Hallermann-Steiff, Goldenhar

Further Testing

OCT through the lesion inferior to the optic disc showed an absence of normal retinal tissue associated with an outpouching of sclera (Figure 3). Additional cuts through the macula confirmed an absence of fluid in the macula.

Abnormal Retinal Appearance
Figure 3

Visual fields showed a superior scotoma corresponding to the inferior lesion in the right eye (Figure 4) and the left eye showed a full field (Figure 5).

Abnormal Retinal Appearance
Figure 4
Posterior Segment Exam
Figure 5

Diagnosis

– The OCT illustrating the absence of retina over the area of abnormal retinal appearance and the visual field showing the superior scotoma strongly suggest a diagnosis of retinochoroidal coloboma. Additionally, the area of abnormal appearance in the optic nerve is consistent with an optic nerve pit. These entities are known to coexist. Given the patient did not have any other systemic pathology, any of the syndromic associations with coloboma, were excluded.

Discussion

Optic nerve pits are excavations of the optic nerve head present from birth. They are believed to originate from incomplete closure of the superior and inferior embryonic fissures. Although benign by natures, the most frequent complication associated with optic nerve pits are serous retinal detachments which are thought to be due to liquefied vitreous gaining access to the subretinal space through the optic nerve pit. Such pits occur in about 1 in 10,000 eyes and 10% of optic nerve pits are bilateral. Optic nerve pits are associated with colobomas of the retina and iris.

Retinochoroidal colobomas are caused by failure of the choroidal fissure to close. Depending on their location, they may be benign or associated with amblyopia, refractive error or visual field defects. They may also be complicated by choroidal neovascularization and retinal detachment. They may be unilateral or bilateral and may be associated with other developmental defects as part of a syndrome.

Combined optic nerve pits and retinochoroidal coloboma are a previously reported entity. They are believed to coexist because they originate from the same failure of fusion. As long as they are in the same eye, they are not known to carry increased risk of a systemic syndrome.

References

Retina, 5th edition, Ryan et al.2013, Chapter 93, 1583-1588

Pagon, RA. Ocular Coloboma, Surv Ophthalmol. 1981:25(4):223-36

Aronowitz P, Judge J. Coloboma of the Optic Disc and Retina. J Gen Intern Med. 2017

Torpedo Maculopathy – July 2017

July 2017

HPI: Patient is a 27 year old woman who was sent for asymptomatic abnormal retina appearance.

PMH:Past medical history was negative. Past ocular history was significant for mild myopia in both eyes. Specifically, she denied any history of trauma to the eyes or any condition needing eye drops.

Exam: Visual acuity was 20/20 in both eyes. IOP and pupils were normal in both eyes. The only abnormality is seen in the right macula as shown in the photographs below.

Right Eye Fundus Appearance
Right Eye Fundus Appearance
left eye fundus appearance
Left Eye Fundus Appearance
Right Eye OCT
Right Eye OCT
Left Eye OCT
Left Eye OCT

Differential Diagnosis

  • Torpedo Maculopathy
  • Best’s Disease
  • Pseudovitelliform Lesion
  • Hyperpigmentation due to past injury, inflammation or infection
  • Pattern Dystrophy
  • Stargardt’s
  • Central Serous Chorioretinopathy

Discussion

Torpedo maculopathy describes a congenital abnormal appearance in the macula of one eye. It is an void hypopigmented area in the temporal macula along the horizontal raphae. These lesions are non-progressive and asymptomatic. They are believed to be related to the fetal bulge of the eye presented in the 4th to 6th months of gestation. They are not associated with other developmental anomalies of the eye or the rest of the body.

The lesions associated with torpedo maculopathy can be associated with OCT changes and hyperautoflourescense but do not require an extensive workup for diagnosis. These patients do not need monitoring beyond that required by dictated by their age, systemic health and other eye conditions.

References

Golchet PR, Jampol LM, Mathura JR, et al Torpedo Maculopathy British Journal of Ophthalmology 2010;94:302-306

Shields CL, Guzman JM, Shapiro MJ, Fogel LE, Shields JA. Torpedo Maculopathy at the Site of the Fetal “Bulge”. Arch Ophthalmol. 2010;128(4):499-501.
doi:10.1001/archophthalmol.2010.29