Atlas and Free Image Companion Website

This is a link to the companion website of "A Compendium of Inherited Diseases of the Eye". These images are provided to you for use in your lectures courtesy of the author and of Oxford University Press. Just click on the cover to go to the website.



 

January 2006

Case 1 - Arterio-Venous Malformation of the Retina
Sophie J. Bakri and Elias I. Traboulsi
Cole Eye Institute
Cleveland Clinic

Case Report

A 12 year old white male was found to have tortuous retinal vessels OD (Figure 1) with a normal retina OS.  There was a small arterio-venous anastomosis from a a superior paramacular retinal artery, connecting with a superior temporal retinal vein (Figure 1).  Another large anastomosis between the superior temporal vein and inferior temporal artery is shown in the late-phase fluorescein angiogram shows an (figure 2). Although the patient had no neurologic signs or symptoms and had full visual fields, neuro-imaging was recommended to rule-out possible intracranial vascular disease, but was refused.



Figure 1: Montage color photograph of the right fundus demonstrates tortuous vessels and arteriovenous vascular connections.



Figure 2: Late-phase fluorescein angiogram shows another anastomosis between the superior temporal vein and inferior temporal artery.

Comment

The patient was diagnosed with Archer’s group 3 retinal arteriovenous anomaly, which, when associated with arteriovenous malformations in the midbrain region is known as Wyburn-Mason syndrome (ref 1) (or Bonnet-Dechaume-Blanc syndrome). In Wyburn-Mason syndrome, vascular malformations have been described along the entire extent of the visual pathway, including the retina, optic nerve, chiasm and tract.  Retinal vascular malformations are congenital and usually unilateral; they are most often found in the temporal retina (ref 2). Perivascular sheathing, exudation, pigmentary degeneration, retinal and vitreous hemorrhages, neovascular glaucoma, and retinal vascular occlusions have been reported in association with these vascular malformations (ref 3).

Cutaneous and neurologic signs were part of the original description of the syndrome by Wyburn-Mason (ref 1), although they are not a constant feature.  The neurologic signs and symptoms are always ipsilateral to the affected eye. The most frequent finding is pyramidal tract involvement (ref 4). Cranial nerve palsies and visual field defects occur commonly, with homonymous hemianopia occurring in 30% of patients. Diagnosis of this retinal lesion mandates prompt referral for neuro-imaging for intracranial arteriovenous malformations.  Wyburn-Mason (ref 1) reported an 81% incidence of intracranial arteriovenous malformation, although the incidence has debated depending on the diagnostic modality. Associated cutaneous abnormalities include nevus flammeus, arteriovenous malformations in the trigeminal nerve distribution and dilation of the vessels on the ipsilateral side of the face (ref 4).  Mild proptosis of the affected eye can occur, possibly due to increased size of the retrobulbar blood vessels, and reducible by manual pressure (ref 4).

References:

1. Wyburn-Mason R: Arteriovenous aneurysm of midbrain and retina, facial nevi and mental changes. Brain 1943; 66:163-203.
2. Mansour AM, Walsh JB, Henkind P.  Arteriovenous anastomoses of the retina. Ophthalmology 1987; 94:35-40.
3. Mansour AM, Wells CG, Jampol LM, Kalina RE. Ocular complications of arteriovenous communications of the retina. Arch Ophthalmol 1989;107:232-6
4. Lecuire J, Dechaume JP, Bret P: Bonnet-Dechaume-Blanc syndrome. In Vinken, PJ and Bruyn, GW, eds: The phakomatoses, vol 14, Handbook of Clinical neurology, Amsterdam, North Holland Publishing Co., 1972.

April 2006

Case 2 - Child with Retinal Dystrophy
Elias I. Traboulsi
Cole Eye Institute
Cleveland Clinic

Case Report

5 y.o.
Nystagmus since birth
Given a diagnosis of rod-cone dystrophy
Extensive metabolic work-up: Negative
Karyotype: Normal
Parents and younger sister: Nl exams
VOU: 1/30
+5.50+1.50x90 OU
Pupils: Normal
Nystagmus
    Intermittent
    Upbeating
A/S: Normal
Fundus: see Figure 1




Figure 1: Posterior pole of left eye shows prominent xanthophyll as well as pigment mottling in macula. Disc is pale and blood vessels are slightly attenuated

Tests

ERG: Non-recordable
LCA gene testing at Carver Lab
    CRB1 mutations:
        Lys801stop
        Cys951Phe (novel)

Comment

The patient has Leber Congenital Amaurosis caused by compound heterozygous mutations in the CRB1 gene. CRB1 mutations account for about 10-15% of LCA. The most common allele, C948Y, is found in the homozygous state only in individuals with LCA [den Hollander et al 2001, Lotery et al 2001]. Other mutations in CRB1 causeretinitis pigmentosa (RP), RP with Coats-like reaction, and RP with preservation of para-arteriolar RPE (PPRPE) [den Hollander et al 1999]. For an extensive review of CRB1-associated LCA please refer to the articles cited below.


References:

den Hollander AI, Heckenlively JR, van den Born LI, de Kok YJ, van der Velde-Visser SD, Kellner U, Jurklies B, van Schooneveld MJ, Blankenagel A, Rohrschneider K, et al. Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. Am J Hum Genet. 2001. 69:198-203.

Jacobson SG, Cideciyan AV, Aleman TS, Pianta MJ, Sumaroka A, Schwartz SB, Smilko EE, Milam AH, Sheffield VC, Stone EM. Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Hum Mol Genet. 2003. 12:1073-8.

Lotery AJ, Jacobson SG, Fishman GA, Weleber RG, Fulton AB, Namperumalsamy P, Heon E, Levin AV, Grover S, Rosenow JR, et al. Mutations in the CRB1 gene cause Leber congenital amaurosis. Arch Ophthalmol. 2001. 119:415-20.

November 2006

Case 3 - Nystagmus and Pupillary Defects
Elias I. Traboulsi
Cole Eye Institute
Cleveland Clinic

Case Report

30 year-old lady presented with nystagmus of unknown etiology. Visual acuity was 20/100 OU. Slit-lamp evaluation showed an indistinct limbus in certain areas and a few scattered subepithelial opacities in the most peripheral part of the cornea. In addition, there was a two-clock hour discontinuity of the pupillary frill (Figure). A diagnosis of Aniridia was suspected and analysis of the PAX6 revealed a C>T mutation in exon 8, changing a CGG to TGG and resulting in an Arg208Trp change in PAX6.



Figure 1: Note indistinct limbus indicating limbal stem cell deficiency and absence of the pupillary frill betwee 2 and 3 o'clock.

Comment

This patient has a very mild form of aniridia. The presence of nystagmus and mild anterior segment malformations such as the ones in this patient should alert the clinician to the possibility of PAX6 mutations. The Arg208Trp (R208W) mutation has been previously reported in aniridia.

References:

Prosser J, van Heyningen V. PAX6 mutations reviewed. Hum Mutat. 1998;11(2):93-108

http://pax6.hgu.mrc.ac.uk/

December 2006

Case 4 - Nystagmus, High Myopia and Retinal Dystrophy in an Infant
Elias I. Traboulsi
Cole Eye Institute
Cleveland Clinic

Case Report

11 month-old girl noted to have nystagmus very early in life. No systemic abnormalities. Normal growth and development. Eye exam shows pendular nystagmus, iris transillumination defects, no cataracts, very blond fundus with fine macular pigmentary changes in one eye (figure 1) and paramacular round chorioretinal defect in the other eye (Figure 2). Clinical considerations were albinism and Leber Congenital Amaurosis. ERG done at Cole Eye Institute - Reduced photopic > photopic amplitudes for age. Further questioning and examination revealed occipital cutaneous defects (Figure 3) that have "filled-up" with time and had been diagnosed as birth marks.



Figure 1: Retcam photo of Left Eye shows very blond fundus and pigmentary changes in macular area.



Figure 2: Retcam photo of Right Eye shows very blond fundus and paramacular chorioretinal defect.



Figure 3: Occipital scalp defects.

Comment

This patient has Knobloch syndrome. This is condition caused by mutations in the COL18A1 gene. Knobloch and Layer described it in a sibship of 10 in which 5  children born to normal non-consanguineous parents had high myopia, vitreoretinal degeneration with retinal detachment and occipital encephaloceles. Since then over 30 patients have been reported. Not all had encephaloceles; some had occipital scalp defects that contain heterotopic neuronal tissue, while others have posterior skull defects or even small intracranial cysts. One patient had an anterior skull and scalp defect. Intelligence is usually normal but autistic behavior and developmental delay have been observed. Uncommon findings include congenital pulmonary lymphangiectasis, patent ductus arteriosus, a single umbilical artery, pyloric stenosis, and the scimitar syndrome.

The gene was mapped to 21q22.3 by Sertie et al., and was identified later as COL18A1 by the same Brazilian group. There is evidence of genetic heterogeneity, at least in one other family.

References:

Knobloch, W. H.; Layer, J. M. : Retinal detachment and encephalocele. J. Pediat. Ophthal. 8: 181-184, 1971.

Sertie, A. L.; Quimby, M.; Moreira, E. S.; Murray, J.; Zatz, M.; Antonarakis, S. E.; Passos-Bueno, M. R. : A gene which causes severe ocular alterations and occipital encephalocele (Knobloch syndrome) is mapped to 21q22.3. Hum. Molec. Genet. 5: 843-847, 1996.

Sertie, A. L.; Sossi, V.; Camargo, A. A.; Zatz, M.; Brahe, C.; Passos-Bueno, M. R. : Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Hum. Molec. Genet. 9: 2051-2058, 2000.

September 2007

Case 5 - Peripheral Pigmentary Retinopathy
Elias I. Traboulsi
Cole Eye Institute
Cleveland Clinic

Case Report

21 y.o.
Blurry vision - Discovered to have pigmentary changes on retinal examination (Figures 1 and 2)
No history of prematurity
Mother has 20/200 vision in one eye from chronic CME
VOU=20/30
Mild hypermetropia
Pupils: Normal
A/S: Normal
Fundus: see Figure 1


Figure: Montage of Right fundus photographs shows clear delineation between areas of normal and abnormal retina with heavy pigmentation in periphery. There are vitreal condensations along the inferonasal vessels.

Tests - ERG: Modestly reduced amplitude with normal implicit times

Diagnosis - ADVIRC - Autosomal Dominant Vitreo-Retino-Choroidopathy

Comment

The diagnosis of ADVIRC is generally based on:
1. Family history
2. Absence of systemic findings
3. Characteristic peripheral pigmentation with posterior clear-cut border with normal appearing retina
4. Variably reduced amplitudes, normal implicit times
5. Variably reduced Arden ratio
6. Very slowly progressive with good visual prognosis

Cataracts and ME are main causes for loss of vision

References:

Blair NP, Goldberg MF, Fishman GA, Salzano T.Autosomal dominant vitreoretinochoroidopathy (ADVIRC).
Br J Ophthalmol. 1984 Jan;68(1):2-9.

Yardley J, Leroy BP, Hart-Holden N, et al. Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant
vitreoretinochoroidopathy (ADVIRC). Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3683-9.

Traboulsi EI, Payne JW. Autosomal dominant vitreoretinochoroidopathy. Report of the third family. 
Arch Ophthalmol. 1993 Feb;111(2):194-6.