hyperopia

Retinoschisis, Juvenile

Clinical Characteristics
Ocular Features: 

Retinoschisis is a retinal disorder characterized by a cystic degeneration of the retina, leading to a split of retinal layers mainly at the level of the nerve fiber layer. Almost all patients have macular involvement, most commonly with foveal spoke-like streaks consisting of microcystic cavities that may coalesce over time. Retinal pigment epithelium atrophy and pigment clumping may occur.  Peripheral schisis is evident in about 50% of patients with large bullous cavities that may resolve spontaneously leaving a pigmented demarcation line. Other retinal findings are white retinal flecks, exudative retinopathy with retinal detachment, perivascular sheathing and dendritiform vessels in the periphery. Vitreous veils are commonly seen that are caused by separation of the thin inner wall of a peripheral schisis cavity and inner wall holes. Bridging vessels may rupture into the cystic cavity or the vitreous. The onset of the disorder has been detected as early as three months, but the majority of cases are five years old or older. Many present with mildly decreased vision that cannot be corrected with glasses and the diagnosis is often delayed. Visual acuity is highly variable ranging from 20/20 to 20/200, but may decline with age and with complications such as vitreous hemorrhage and macular detachment.  The disorder is also associated with axial hyperopia, posterior subcapsular cataract and strabismus. Fluorescein angiography shows minimal or no leakage as opposed to cystoid macular edema. Focal areas of vascular leakage into schisis cavity may be present as well as peripheral capillary nonperfusion. Electroretinograms exhibit a reduced b-wave and a preserved a-wave.

Systemic Features: 

No general systemic manifestations are associated with juvenile retinoschisis.

Genetics

Juvenile retinoschisis is an X-linked recessive disorder that affects mainly males. The causative mutations involve the gene RS1 located on the X chromosome at Xp22. Female carriers may have peripheral schisis amd many allelic variants have been reported.  The encoded protein retinoschisin is a secreted protein produced by photoreceptors and bipolar cells and may be involved in cell-cell adhesion or ion channel regulation.

Treatment
Treatment Options: 

There is presently no effective treatment for the disorder, but decreased vision later in life can be aided with low vision aids. Cases with posterior subcapsular cataract can be treated with cataract extraction.  Improvement in the cystic macular lesions, central foveal zone thickness, and visual acuity have been reported to benefit from topical dorzolamide treatment.

References
Article Title: 

Peripheral fundus findings in X-linked retinoschisis

Fahim AT, Ali N, Blachley T, Michaelides M. Peripheral fundus findings in X-linked retinoschisis. Br J Ophthalmol. 2017 Mar 27. pii: bjophthalmol-2016-310110. doi: 10.1136/bjophthalmol-2016-310110. [Epub ahead of print].

PubMed ID: 
28348004

X-linked retinoschisis: an update

Sikkink SK, Biswas S, Parry NR, Stanga PE, Trump D. X-linked retinoschisis: an update. J Med Genet. 2007 Apr;44(4):225-32. 2006 Dec 15.

PubMed ID: 
17172462

Cornea Plana

Clinical Characteristics
Ocular Features: 

Enlargement of the cornea with flattening is characteristic of cornea plana although corneal diameters vary widely.  Corneal thinning may be present.  The mean corneal refraction value at the horizontal median has been measured at 37.8 D for the dominant form (CNA 1) of the disease, compared with 29.9 D for the recessive form (CNA 2) and 43.4 D for controls accounting for the hyperopia found among many patients.  The limbal margin may be widened with blurring of the corneolimbal junction.  Recessive cases can often be distinguished from the dominant ones by the presence of a central 5 mm area of thickening and clouding.  Recessively inherited cases are also more likely to have anterior synechiae and other iris anomalies.  Early onset arcus has been reported.

Vision in mild cases may be as good as 20/25 or 20/30 but considerably worse in recessive cases with central opacification.  Glaucoma may occur in older individuals.

Systemic Features: 

None reported.

Genetics

Multiple families in Finland have been reported with inheritance patterns suggesting autosomal recessive inheritance (CNA2).  The gene has been mapped to chromosome 12 (12q21) in a region containing the KERA gene.  A Cuban family with autosomal dominant cornea plana (CDA1) also yielded linkage to 12q where the recessive gene is located.  However, this locus could be excluded in two Finnish families suggesting that at least 3 autosomal mutations may be responsible.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

Correction of the hyperopia may be helpful.  Patients need to be followed and treated for glaucoma if it develops.  Outcomes of penetrating keratoplasty are not available but the procedure carries increased risk since the stroma is often thinner than normal. 
 

References
Article Title: 

The genetics of cornea plana congenita

Tahvanainen, E.; Forsius, H.; Kolehmainen, J.; Damsten, M.; Fellman, J.; de la Chapelle, A. :  The genetics of cornea plana congenita. J. Med. Genet. 33: 116-119, 1996.

PubMed ID: 
8929947

Mutations in KERA, encoding keratocan, cause cornea plana

Pellegata, N. S.; Dieguez-Lucena, J. L.; Joensuu, T.; Lau, S.; Montgomery, K. T.; Krahe, R.; Kivela, T.; Kucherlapati, R.; Forsius, H.; de la Chapelle, A. :  Mutations in KERA, encoding keratocan, cause cornea plana. Nature Genet. 25: 91-95, 2000.

PubMed ID: 
10802664

Macular Dystrophy, Vitelliform 2

Clinical Characteristics
Ocular Features: 

Best disease primarily affects the macular and paramacular areas.  The classical lesion resembles an egg yolk centered on the fovea.  Most patients, however, never exhibit the typical vitelliform lesion and may instead have normal maculae, or irregular yellowish deposits that may even be extrafoveal.  Histologically the RPE contains increased amounts of lipofuscin.  The ‘egg yolk’ is located beneath the neurosensory retina and the overlying retinal circulation often remains intact.  It can evolve into a ‘scrambled egg’ appearance and an apparent fluid level may be evident.  Some patients exhibit only RPE changes including hyper-  or hypopigmentation throughout the macula.  Choroidal neovasculariztion with hemorrhage leading to scarring and gliosis are uncommon but present a serious risk to vision.  The common end point for symptomatic patients is some degree of photoreceptor damage.

Until recently, most reports of Best macular dystrophy did not include genotypic data.  It is therefore difficult to classify families with variants of the disease, such as adult-onset or atypical vitelliform dystrophy but these at least suggest that this may be a heterogeneous disorder.  At the present time, the diagnosis should be reserved for those with an abnormal light-to-dark (Arden) ratio on electro-oculography and a mutation in the BEST1 gene. 

Visual function varies widely and has considerable fluctuation.   As many as 7-9 percent of patients are asymptomatic throughout life and few have vision loss to 20/200.  Many individuals maintain vision of 20/40 or better throughout life.  Some experience episodic acute vision loss to 20/80 or worse but often recover to at least 20/30.  It has been reported that as many as 76 per cent under the age of 40 retain 20/40 and 30 per cent retain this level of vision into the 5th and 6th decade of life.

Other ocular manifestations include hyperopia, esotropia, and, rarely, shallow anterior chambers with angle closure glaucoma.

Systemic Features: 

None have been reported.

Genetics

A mutation in the bestrophin gene (BEST1) located on chromosome 11 (11q13) is responsible for the disease in most patients.  Best disease is usually transmitted in an autosomal dominant pattern from parent to offspring.  A large number of mutations have been found in the BEST1 gene but so far no correlation with severity of disease is possible.  In fact, there is a great deal of clinical variation within families having identical mutations resembling that of the variation found among different mutations.

Several families have also been reported with autosomal recessive inheritance.  Affected offspring had homozygous mutations in the bestrophin gene with reduced light/dark responses and vision loss.  Some have atypical vitelliform retinal and sometimes multifocal lesions.  They may develop angle closure glaucoma.  Their heterozygous parents  have either normal or abnormal EOGs and no visible fundus disease.  So far no families with presumed recessive inheritance of Best macular dystrophy have demonstrated parent-to-child transmission of typical vitelliform lesions.

Genotyping has identified at least 5 forms of vitelliform macular dystrophy.  In addition to the iconic Best disease described here we know of at least four more variants and specific mutations have been identified in three.  No mutation or locus has yet been identified in VMD1 (153840) but it is likely a unique condition since mutations in other genes known to cause vitelliform dystrophy have been ruled out.  Other forms are VMD3 (608161) due to mutations in the PRPH2 gene, VMD4 (616151) resulting from mutations in the IMPG1 gene, and VMD5 (616152) caused by mutations in the IMPG2 gene.

Autosomal dominant vitreoretinochoroidopathy (193220) is an allelic disorder.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

None known for disease.  Subretinal neovascularization may benefit from ablation treatments.

References
Article Title: 

Mutations in IMPG1 Cause Vitelliform Macular Dystrophies. Am

Manes G, Meunier I, Avila-Fern?degndez A, Banfi S, Le Meur G, Zanlonghi X, Corton M, Simonelli F, Brabet P, Labesse G, Audo I, Mohand-Said S, Zeitz C, Sahel JA, Weber M, Dollfus H, Dhaenens CM, Allorge D, De Baere E, Koenekoop RK, Kohl S, Cremers FP, Hollyfield JG, S?(c)n?(c)chal A, Hebrard M, Bocquet B, Garc??a CA, Hamel CP. Mutations in IMPG1 Cause Vitelliform Macular Dystrophies. Am J Hum Genet. 2013 Aug 29. [Epub ahead of print] PubMed PMID: 23993198.

PubMed ID: 
23993198

Biallelic mutation of BEST1 causes a distinct retinopathy in humans

Burgess R, Millar ID, Leroy BP, Urquhart JE, Fearon IM, De Baere E, Brown PD, Robson AG, Wright GA, Kestelyn P, Holder GE, Webster AR, Manson FD, Black GC. Biallelic mutation of BEST1 causes a distinct retinopathy in humans. Am J Hum Genet. 2008 Jan;82(1):19-31. PubMed PMID: 18179881

PubMed ID: 
18179881

Identification of the gene responsible for Best macular dystrophy

Petrukhin K, Koisti MJ, Bakall B, Li W, Xie G, Marknell T, Sandgren O, Forsman K, Holmgren G, Andreasson S, Vujic M, Bergen AA, McGarty-Dugan V, Figueroa D, Austin CP, Metzker ML, Caskey CT, Wadelius C. Identification of the gene responsible for Best macular dystrophy. Nat Genet. 1998 Jul;19(3):241-7.

PubMed ID: 
9662395

Pages

Subscribe to RSS - hyperopia