retinal exudates

Familial Exudative Vitreoretinopathy, EVR7

Clinical Characteristics
Ocular Features: 

The ocular features are primarily limited to the posterior chamber where there are areas of retinal avascularity, exudation, retinal holes, and detachments.  Areas of degeneration and pigmentary retinopathy may be present.  Vascular proliferation may be part of the process with vitreous traction and folds.  Progression of retinal damage is highly variable and surgical outcomes are unpredictable.  Long term vision outcomes are sometimes as good as 20/40 but in many eyes NLP or hand motion vision is the end result.  

Secondary changes in the anterior chamber and cornea from repeated surgeries may lead to glaucoma, cataracts, and corneal decompensation. 

Systemic Features: 

There are no consistent systemic abnormalities.

Genetics

Missense and nonsense heterozygous mutations in the CTNNB1 gene (3p22.1) segregate with this autosomal dominant condition found in two families of Japanese origin.  A Chinese 3-year-old with FEVR having a single BP insertion in the CTNNB1 gene also had global developmental delay and dysmorphic facies.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

The prognosis for vision is poor as the retinal damage often continues to evolve and additional folds and detachments develop.  Attempts to close retinal holes and repair detachments are important.

References
Article Title: 

Defects in the Cell Signaling Mediator β-Catenin Cause the Retinal Vascular Condition FEVR

Panagiotou ES, Sanjurjo Soriano C, Poulter JA, Lord EC, Dzulova D, Kondo H, Hiyoshi A, Chung BH, Chu YW, Lai CHY, Tafoya ME, Karjosukarso D, Collin RWJ, Topping J, Downey LM, Ali M, Inglehearn CF, Toomes C. Defects in the Cell Signaling Mediator v-Catenin Cause the Retinal Vascular Condition FEVR. Am J Hum Genet. 2017 Jun 1;100(6):960-968.

PubMed ID: 
28575650

Coats Plus Syndrome

Clinical Characteristics
Ocular Features: 

Retinal telangiectasia and exudates (Coats disease) occur in association with intracranial cysts, calcifications and extraneurologic manifestations in this condition.  Coats disease lesions may also occur in Labrune syndrome (614561) and, of course, in isolation.

Whereas simple Coats disease almost exclusively occurs unilaterally and in males, both sexes and both eyes may have Coats retinal lesions in this syndrome.

Systemic Features: 

As a result of intracranial calcifications, leukodystrophy and brain cysts, patients have a variety of neurologic signs including spasticity, ataxia, dystonia, cognitive decline, and seizures.  Vascular ectasias may also occur throughout the body such as the intestines, stomach, and in the liver increasing the risk of GI bleeding and portal hypertension with anemia and thrombocytopenia.  Some individuals have sparse hair, abnormal pigmentation of the skin, and dysplastic nails as well. 

Some extraretinal features are also found in patients with dyskeratosis congenita (127550), and in Labrune syndrome (614561).

Genetics

This autosomal recessive pleotropic disorder results from compound heterozygous mutations in the CTC1 gene (17p13.1).  Several patients with mutations in STN1 have also been reported.

Most cases of simple Coats disease occur sporadically.  No associated locus or mutation has been found.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment for the general condition has been reported.  Specific treatment for the retinal vascular and brain lesions might be of benefit.  Physical therapy and special education should be considered in selected patients.

References
Article Title: 

Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. J Exp Med. 2016 Jul 25;213(8):1429-40

Simon AJ, Lev A, Zhang Y, Weiss B, Rylova A, Eyal E, Kol N, Barel O, Cesarkas K, Soudack M, Greenberg-Kushnir N, Rhodes M, Wiest DL, Schiby G, Barshack I, Katz S, Pras E, Poran H, Reznik-Wolf H, Ribakovsky E, Simon C, Hazou W, Sidi Y, Lahad A, Katzir H, Sagie S, Aqeilan HA, Glousker G, Amariglio N, Tzfati Y, Selig S, Rechavi G, Somech R. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. J Exp Med. 2016 Jul 25;213(8):1429-40.

PubMed ID: 
27432940

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Anderson BH, Kasher PR, Mayer J, Szynkiewicz M, Jenkinson EM, Bhaskar SS, Urquhart JE, Daly SB, Dickerson JE, O'Sullivan J, Leibundgut EO, Muter J, Abdel-Salem GM, Babul-Hirji R, Baxter P, Berger A, Bonafe L, Brunstom-Hernandez JE, Buckard JA, Chitayat D, Chong WK, Cordelli DM, Ferreira P, Fluss J, Forrest EH, Franzoni E, Garone C, Hammans SR, Houge G, Hughes I, Jacquemont S, Jeannet PY, Jefferson RJ, Kumar R, Kutschke G, Lundberg S, Lourenco CM, Mehta R, Naidu S, Nischal KK, Nunes L, Ounap K, Philippart M, Prabhakar P, Risen SR, Schiffmann R, Soh C, Stephenson JB, Stewart H, Stone J, Tolmie JL, van der Knaap MS, Vieira JP, Vilain CN, Wakeling EL, Wermenbol V, Whitney A, Lovell SC, Meyer S, Livingston JH, Baerlocher GM, Black GC, Rice GI, Crow YJ. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet. 2012 Jan 22;44(3):338-42.

PubMed ID: 
22267198

Familial Exudative Vitreoretinopathy, EVR6

Clinical Characteristics
Ocular Features: 

Clinical features of this type of exudative retinopathy are based upon the findings in a single large Dutch pedigree containing 16 affected individuals.  The age of onset is unknown but this condition has been described in a 3 year old.  Characteristics of FEVR6 are often seen in individuals during the second or third decades when decreasing vision becomes a challenge.  While some individuals can have normal acuity, others have severe vision loss, often to finger-counting range.

Ocular findings are limited to the fundus consisting of areas of hypo- or hyperpigmentation, dragging of the macula, peripheral retinal avascularity, leaky and stretched capillaries, and exudates.  There may be falciform retinal folds and detachments.  Some patients have white masses of fibrous tissue in or overlying the retina.  Cataracts have been described in several patients.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

FEVR6 results from heterozygous mutations in the ZNF408 gene (11p11.2).  Homozygous mutations in the same gene are responsible for retinitis pigmentosa 72 (616469).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Retinal detachment surgery, while technically difficult, may provide some benefit.

References
Article Title: 

ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature

Collin RW, Nikopoulos K, Dona M, Gilissen C, Hoischen A, Boonstra FN, Poulter JA, Kondo H, Berger W, Toomes C, Tahira T, Mohn LR, Blokland EA, Hetterschijt L, Ali M, Groothuismink JM, Duijkers L, Inglehearn CF, Sollfrank L, Strom TM, Uchio E, van Nouhuys CE, Kremer H, Veltman JA, van Wijk E, Cremers FP. ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9856-61.

PubMed ID: 
23716654

Familial Exudative Vitreoretinopathy, EVR3

Clinical Characteristics
Ocular Features: 

Abnormal retinal angiogenesis with retinal ischemia is the development defect that leads to the clinical features of the familial exudative vitreoretinopathies.  It is usually bilateral.  There is considerable clinical heterogeneity in the appearance of both the retina and the vitreous but common to all is the presence of peripheral areas of avascularity in the retina that may be seen in newborns.  This may only be visible using fluorescein angiography in mild cases.  The vessels may be hyperpermeable resulting in patchy exudates in the retina.  Neovascularization often develops with retinal and vitreous bleeding and eventually retinal traction resulting in retinal folds and detachments. Severe disease with early onset may result in blindness in infants but milder disease may be asymptomatic even as adults.  Cataracts may result.

The ocular disease may be confused with retinal dysplasia (as seen in pseudogliomas and Norrie disease [310600]) or retinopathy of prematurity.

Systemic Features: 

 No systemic features have been reported in EVR3.

Genetics

This is likely an autosomal dominant disorder based on pedigree evidence but no specific mutation has been found.  A disease locus at 11p13-p12 has been identified by linkage studies, located near the FZD4 gene containing the mutation responsible for EVR1.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Appropriate vitreoretinal surgery to release vitreous traction and to repair retinal detachments should be considered.  Cataract removal may be beneficial.  Low vision aids could be helpful in milder cases with residual vision.

References
Article Title: 

Familial Exudative Vitreoretinopathy, EVR5

Clinical Characteristics
Ocular Features: 

The clinical picture is highly heterogeneous.  Abnormal peripheral vascularization of the retina is generally evident and most individuals have retinal exudates.  The amount of exudation is dependent to some extent upon age.  Fluorescein angiography may demonstrate incomplete vascularization of the peripheral retina.  The ocular phenotype can resemble retinal dysplasia.  Occasional infants can have severe retinal disease and may be considered blind but many individuals have minimal disease and retain good vision into adulthood.  Unfortunately, traction retinal detachments may develop at any time and are responsible for blindness in some patients. 

Cataracts are sometimes present. Ectopic pupils, lack of well-defined pupillary collarettes, remnants of the fetal vascular stalk, and shallowing of the anterior chamber have been noted in several patients.  Microphthalmia and corneal opacities may also be present.  Horizontal nystagmus can be seen in severely affected babies before one month of age.

Systemic Features: 

No systemic features have been reported.

Genetics

This disorder can be inherited in an autosomal dominant pattern as the result of heterozygous mutations in the TSPAN12 gene (7q31.31).  However, individuals with more severe disease may have homozygous mutations in this gene. 

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

This disorder can be inherited in an autosomal dominant pattern as the result of heterozygous mutations in the TSPAN12 gene (7q31.31).  However, individuals with more severe disease may have homozygous or compound heterozygous mutations in this gene. 

References
Article Title: 
Subscribe to RSS - retinal exudates