optic neuropathy

Glaucoma, Open Angle, Primary

Clinical Characteristics
Ocular Features: 

It has long been known from both clinical and genetic criteria that the disease called glaucoma is a heterogeneous condition. The common denominator is considered to be an optic neuropathy for which the primary risk factor is an elevation of intraocular pressure. However, the well-known clinical profile of glaucomatous retinal and optic nerve damage can also be found among patients without increased IOP and for these the cause remains elusive.  Ultimately, damage to retinal neurons and their axons result in loss of visual field and optic nerve volume with eventual blindness if untreated.

Systemic Features: 

No systemic abnormalities are consistently associated with primary open angle glaucoma.  However, glaucoma occurs in a large number of ocular and systemic disorders as well as chromosomal aberrations and in many such conditions there are anatomic abnormalities in the anterior chamber angle.  A variety of mainly anecdotal risk factors such as obesity, smoking, diabetes, migraines, stress and cardiovascular disease have been reported but their causative relationships have not been established.

Genetics

Primary open angle glaucoma likely consists of a collection of disorders resulting from an optic neuropathy.  Based on family data and ethnic distribution there can be little doubt that genes influence susceptibility to this disease.  In fact, 13 types have been described based on the unique chromosomal locations of mutations that have been associated with each.   Mutations in MYOC (1q23-q24) are responsible for a substantial proportion of POAG cases known as GLC1A through as yet unknown mechanisms.  Others types labeled GLC1B through GLC1O may result from specific mutations located on 10 different chromosomes.  In the absence of pedigrees with typical Mendelian inheritance patterns, it is reasonable to consider that the genes reported to be associated with POAG so far simply confer susceptibility to the optic neuropathy characteristic of clinical glaucoma (for further discussion see 137760).  Unidentified environmental factors in combination with other genes in individual genomes likely determine the degree of susceptibility in each person. 

Treatment
Treatment Options: 

Lowering of intraocular pressure remains the only clinical treatment available to lower the risk of POAG.  Unfortunately, this is not always effective, especially when the intraocular pressure is not significantly elevated.  There are no infallible guidelines for optimum pressure control and the therapy regimen must be tailored by follow-up monitoring of visual field and optic cup changes.  Once established, it is a lifelong disorder that requires active management.

Early detection is important in the management of glaucoma.  It is largely a 'silent' disease and the eye care professional cannot assume that absence of symptoms correlates with absence of disease.  A family history of glaucoma, especially in first degree relatives, as well as African American, Native American, and Hispanic ethnicity, and increased age are associated with an elevated risk of open angle glaucoma.  Patients belonging to such high risk groups should be monitored with regular examinations.

References
Article Title: 

Variants in the PRPF8 Gene are Associated with Glaucoma

Micheal S, Hogewind BF, Khan MI, Siddiqui SN, Zafar SN, Akhtar F, Qamar R, Hoyng CB, den Hollander AI. Variants in the PRPF8 Gene are Associated with Glaucoma. Mol Neurobiol. 2017 Jul 13. doi: 10.1007/s12035-017-0673-5. [Epub ahead of print].

PubMed ID: 
28707069

Open-angle glaucoma

Quigley HA. Open-angle glaucoma. N Engl J Med. 1993 Apr 15;328(15):1097-106. Review.

PubMed ID: 
8455668

Glaucoma, Pigment Dispersion Syndrome

Clinical Characteristics
Ocular Features: 

This is a form of open angle glaucoma with early onset (usually before the age of 40 years).  Marked pigment deposition in the trabecular meshwork, on the lens, zonules, and the corneal endothelium can often be seen prior to elevation of the intraocular pressure. It can be present asymmetrically, even unilaterally, but primarily in early stages.  The pigment source in humans seems to be the iris in which hypopigmentation leads to radial transillumination defects and mouse models corroborate this.  The iris configuration is sometimes described as flat or even concave.  The pattern of pigment deposition on the posterior surface of the cornea is known as a Krukenberg spindle and considered diagnostic.  Untreated, the characteristic optic nerve damage and visual field changes of glaucoma eventually occur.  Early-onset and rapidly progressive nuclear cataracts have been reported in some patients.

In one longitudinal study of 113 patients diagnosed with pigment dispersion and followed for 24 years, 23 had glaucoma initially and 9 more eventually required treatment for elevated pressure. The mean age at diagnosis was 42 years and myopic males were the most commonly affected.

The syndromic nature of PDS is suggested by the association of lattice degeneration, retinal tears, and detachments in a significant number of individuals.

Systemic Features: 

No systemic disease has been reported.

Genetics

This is an autosomal dominant form of glaucoma-related optic neuropathy that shares some features with open angle juvenile glaucoma (137750), such as myopia and early onset.  The pigment dispersion syndrome described here, however, maps to a different locus (7q35-q36).  Another candidate locus is located at 18q11-q21 but the causative mutations remain elusive.

A four generation family with an apparent autosomal recessive pattern has been reported.

The autosomal dominant pattern is not always apparent from history alone and examination of relatives is necessary to document the familial nature of this disease. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

The usual glaucoma therapies are indicated.  Some have advised limiting vigorous impact sports to reduce the amount of pigment released.  All individuals with pigment dispersion must be followed vigilantly for development of glaucoma as the risk is high.  It has been estimated to be 10% within 5 years and 15% in 15 years, regardless of age and family history.  Further, the pigment dispersion is progressive along with the risk of elevated pressure as eventually 30 -50% of patients develop glaucoma.  However, regression of pigment deposition, decrease of iris transillumination and even stabilization of pressure has also been noted in some, mostly younger, patients.

Laser iridotomy has been suggested as therapeutically useful in the reduction of the IOP but there is no statistical confirmation of this.

References
Article Title: 
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