macular edema

Retinopathy with Neutropenia

Clinical Characteristics
Ocular Features: 

Pigmentary retinopathy was reported in a 25 year old female with moderately reduced visual acuity. Rare bone spicules pigment deposits were present in the periphery and macular edema was noted. Severely reduced scotopic and photopic responses were recorded.

Systemic Features: 

The single reported individual had congenital neutropenia and microcephaly. She had evident growth retardation and microcephaly at birth with subsequent recurrent upper respiratory infections and gingivitis. Speech and motor development were normal. Short stature was noted as well. The limbs were described as slender as in Cohen syndrome (216550) but no truncal obesity or joint hypermobility was present. The facial dysmorphism only vaguely resembled that found in Cohen syndrome (216550).

Genetics

This is a newly described condition whose unique identity remains to be established since only a single patient has been reported. This patient carried two heterozygous splicing mutations in the same VPS13B gene, the same gene in which more than 100 homozygous mutations have been found in individuals with Cohen syndrome (216550). Each parent carried a different splicing mutation in VPS13B.

Cohen syndrome (216550) however, has additional phenotypic features such as truncal obesity, intellectual disabilities, intermittent neutropenia, microcephaly, facial dysmorphism, myopia, and progressive chorioretinal dystrophy. Variable amounts of neutropenia were observed from age 5 years but the marrow was normocellular in appearance.

Isolated retinopathy with neutropenia may or may not be an autosomal recessive variant of Cohen syndrome (216550).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Macular Edema, Autosomal Dominant Cystoid

Clinical Characteristics
Ocular Features: 

Only a few families have been reported.  The macular edema can be traced to retinal capillary leakage throughout the posterior pole as revealed by fluorescein angiography.  Scattered exudates and nerve fiber layer hemorrhages are sometimes seen.  Hyperopia and strabismus are often present as well.  Veils, strands, and white punctate deposits in the vitreous have been described.  Wrinkling of the internal limiting membrane may be present.  The ERG is normal except for elevated rod dark adaptation thresholds.  Light/dark ratios are abnormal on EOG testing and mild dyschromatopsia can be demonstrated.  Patients usually notice problems with their visual acuity in the second decade of life and it can drop to 20/200 at this time with progression to 2/120 - 2/200 in older individuals.  In later stages of the disease a central zone of beaten bronze macular atrophy can be seen.  Surrounding this central atrophy is often an area with pigmentary changes resembling retinitis pigmentosa which can extend into the periphery.

This would seem to be a unique disorder in spite of some similarities to retinitis pigmentosa in which macular cysts are often seen.  The clinical course is distinctly different and the presence of vitreous deposits and hyperopia also can be used as arguments for its separateness.  Molecular DNA evidence showing lack of allelism (Vida infra) is, of course the strongest evidence.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This autosomal dominant form of progressive macular dystrophy is linked to a locus at 7p21-p15.  The mutation is close to the RP9 locus causing one type of retinitis pigmentosa but linkage analysis shows the two disorders to be non-allelic.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No specific treatment is available for the macular disease but low vision aids are likely useful, at least early in the disease.

References
Article Title: 

Retinitis Pigmentosa, AR

Clinical Characteristics
Ocular Features: 

The term retinitis pigmentosa is applied to a large group of disorders with great clinical and genetic heterogeneity.  The ocular disease is characterized by night blindness, field constriction, and pigmentary changes in the retina.  The latter is sometimes described as having a ‘bone corpuscle’ appearance with a perivascular distribution.  A ring scotoma is usually evident.  Age of onset and rate of progression is highly variable, even within families.  The rods are impacted early but cone deterioration with loss of central vision usually follows.  Some patients complain of dyschromatopsia and photophobia.  The ERG generally documents this progression but the mfERG shows wide variations in central cone functioning.  Legal blindness is common by the 5thdecade of life or later.  The course of clinical and ERG changes is more aggressive in the X-linked form than in the autosomal dominant disease.  The final common denominator for all types is first rod and then cone photoreceptor loss through apoptosis.

As many as 50% of patients develop posterior subcapsular cataracts.  The vitreous often contains cells and particulate debris.   Retinal arterioles are often attenuated and the optic nerve may have a waxy pallor, especially late in the disease.  Occasional patients have cysts in the macula.  Some patients experience continuous photopsia. 

Systemic Features: 

The ‘simple’ or nonsyndromal type of RP described here has no systemic features.  However, the retinopathy is seen in a number of syndromes and, of course, in some infectious diseases as well.  It is more accurate to label the fundus finding as 'pigmentary retinopathy' in such cases.

Genetics

A significant proportion of RP cases occur sporadically, i.e., without a family history.  Mutations in more than 30 genes cause autosomal recessive RP disorders and these account for more than half of all cases of retinitis pigmentosa.  More than 100 mutations have been identified in the RHO gene (3q21-q24) alone.  Mutations in some genes cause RP in both autosomal recessive and autosomal dominant inheritance patterns.  Compound heterozygosity is relatively common in autosomal recessive disease.  See OMIM 268000 for a complete listing of mutations.

Many genes associated with retinitis pigmentosa have also been implicated in other pigmentary retinopathies.  In addition, numerous phenocopies occur, caused by a variety of drugs, trauma, infections and numerous neurological disorders.  To make diagnosis even more difficult, the fundus findings and ERG responses in nonsyndromic RP in most patients are too nonspecific to be useful for classification. Extensive systemic and ocular evaluations are important and should be combined with genotyping in both familial and nonfamilial cases to determine the diagnosis and prognosis. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Photoreceptor transplantation has been tried in without improvement in central vision or interruption in the rate of vision loss.  Longer term results are needed.  Resensitizing photoreceptors with halorhodopsin using archaebacterial vectors shows promise in mice.  High doses of vitamin A palmitate slow the rate of vision loss but plasma levels and liver function need to be checked at least annually.  Oral acetazolamide can be helpful in reducing macular edema.

Low vision aids and mobility training can be facilitating for many patients.  Cataract surgery may restore several lines of vision, at least temporarily.

Several pharmaceuticals should be avoided, including isotretinoin, sildenafil, and vitamin E. 

References
Article Title: 

Retinitis Pigmentosa, AD

Clinical Characteristics
Ocular Features: 

Retinitis pigmentosa is a large group of disorders with great clinical and genetic heterogeneity.  The ocular disease is characterized by night blindness, field constriction, and pigmentary changes in the retina.  The later may have a 'bone corpuscle' appearance with a perivascular distribution.  A ring scotoma is sometimes evident.  Age of onset and rate of progression is highly variable, even within families.  The rods are impacted early but cone deterioration with loss of central vision usually follows.  Some patients complain of dyschromatopsia and photophobia.  The ERG generally documents this progression but the mfERG shows wide variations in central cone functioning.  Legal blindness is common by the 5thdecade of life or later.  The course of clinical and ERG changes is more aggressive in the X-linked form than in the autosomal dominant RHO disease.  The final common denominator for all types is first rod and then cone photoreceptor loss through apoptosis.

As many as 50% of patients develop posterior subcapsular cataracts.  The vitreous often contains cells and particulate debris.   Retinal arterioles are often attenuated and the optic nerve may have a waxy pallor, especially late in the disease.  Occasional patients have cysts in the macula.  Some patients experience continuous photopsia.  

Systemic Features: 

The 'simple' or nonsyndromal type of RP described here has no systemic features.  However, the retinopathy is seen in a number of syndromes and, of course, in trauma and in some infectious diseases as well. 

Genetics

A significant proportion of RP cases occur sporadically, i.e., without a family history.  Mutations in more than 25 genes cause autosomal dominant RP disorders and these account for about one-third of all cases of retinitis pigmentosa but there are many more specific mutations.  More than 100 have been identified in the RHO gene (3q21-q24) alone, for example.  Mutations in some genes cause RP in both autosomal recessive and autosomal dominant inhritance patterns.  See OMIM 268000 for a complete listing of mutations.

Many genes associated with retinitis pigmentosa have also been implicated in other pigmentary retinopathies.  In addition numerous phenocopies occur, caused by a variety of drugs, trauma, infections and numerous neurological disorders.  To make diagnosis even more difficult, the fundus findings and ERG responses in nonsyndromic RP in most patients are too nonspecific to be useful for classification. Extensive systemic and ocular evaluations are important and should be combined with genotyping in both familial and nonfamilial cases to determine the diagnosis and prognosis. 

For autosomal dominant retinitis pigmentosa resulting from mutations in RP1, see Retinitis Pigmentosa 1 (180100). 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Photoreceptor transplantation has been tried in 8 patients without improvement in central vision or interruption in the rate of vision loss.  Longer term results are needed.  Resensitizing photoreceptors with halorhodopsin using archaebacterial vectors shows promise in mice.  High doses of vitamin A palmitate slow the rate of vision loss but plasma levels and liver function need to be checked at least annually.  The use of oral and systemic carbonic anhydrase inhibitors can be helpful in reducing macular edema.

Low vision aids and mobility training can be facilitating for many patients.  Cataract surgery may restore several lines of vision at least temporarily.

Several pharmaceuticals should be avoided, including isotretinoin, sildenafil, and vitamin E. 

References
Article Title: 

Retinitis Pigmentosa 3, X-Linked

Clinical Characteristics
Ocular Features: 

Retinitis pigmentosa is a large group of disorders with great clinical and genetic heterogeneity.  The ocular disease is characterized by night blindness, field constriction, and pigmentary changes in the retina.  The later may have a ‘bone corpuscle’ appearance with a perivascular distribution.  A ring scotoma is sometimes evident.  Age of onset and rate of progression is highly variable, even within families.  In this, an X-linked form of the disease, the first symptoms often appear early in the second decade of life.  The rods are impacted early but cone deterioration with loss of central vision usually follows.  Some patients complain of dyschromatopsia and photophobia.  The ERG generally documents this progression but the mfERG shows wide variations in central cone functioning.  Legal blindness is common by the 4thor 5thdecades of life.  The course of clinical and ERG changes is more aggressive in the X-linked form than in autosomal dominant retinitis pigmentosa disease resulting from RHO mutations.  The final common denominator for all types is first rod and then cone photoreceptor loss through apoptosis.

Up to 50% of adults develop cataracts beginning in the posterior subcapsular area.  The vitreous often contains cells and some patients have cystoid macular edema.  A waxy pallor of the optic nerve is sometimes present especially in the later stages of the disease.

Female carriers generally are asymptomatic but may also have severe RP.  Occasionally they have an unusual tapetal reflex consisting of a ‘beaten metal’ appearance or sometimes scintillating, golden patches. 

Systemic Features: 

There is no systemic disease in ‘simple’ or non-syndromic retinitis pigmentosa but pigmentary retinopathy is associated with a number of syndromes (syndromal RP) e.g.,  Usher syndromes, Waardenburg syndrome, Alport syndrome, Refsum disease, Kerns-Sayre syndrome, abetalipoproteinemia, neuronal ceroid lipofuscinosis, mucopolysaccharidoses types I, II, III, and Bardet-Biedl syndromes. 

The RPGR gene is important to the normal function of cilia throughout the body.  For this reason disorders resulting from RPGR mutations such as CORDX1 (304020) and this one are sometimes classified as primary ciliary dyskinesias or ciliopathies.  The gene products of the RPGR gene, for example, are localized to connecting cilia of the outer segments of rods and cones and in motile cilia in the airway epithelia.  A subset of families with RP3 have chronic and recurrent upper respiratory infections including sinusitis, bronchitis, pulmonary atelectasis, and otitis media (300455) similar to that seen in the immotile cilia syndrome (244400).  Female carriers in these families have few retinal changes but may suffer recurrent and severe upper respiratory infections similar to hemizygous males.  Severe hearing loss also occurs in both sexes with the RPGR mutations and there is some evidence that this may be a primary sensorineural problem, perhaps in addition to conductive loss from recurrent otitis media.

Genetics

Mutations in more than 100 genes may be responsible for retinitis pigmentosa but sporadic disease occurs as well.  Between 5 and 10% of individuals have X-linked disease.  Perhaps 70% of X-linked RP is caused by mutations in RPGR (Xp11.4) as in this condition.  The same gene is mutant in one form of X-linked cone-rod dystrophy (CORDX1; 304020). These  disorders are sometimes considered examples of X-linked ocular disease resulting from a primary ciliary dyskinesia (244400).

Another form of X-linked RP (RP2) with more choroidal involvement is caused by mutations in the RP2 gene (312600 ; Xp11.23). 

Many genes associated with retinitis pigmentosa have also been implicated in other pigmentary retinopathies.  In addition numerous phenocopies occur, caused by a variety of drugs, trauma, infections and numerous neurological disorders.  To make diagnosis even more difficult, the fundus findings and ERG responses in nonsyndromic RP in most patients are too nonspecific to be useful for classification. Extensive systemic and ocular evaluations are important and should be combined with genotyping in both familial and nonfamilial cases to determine the diagnosis and prognosis. 

Treatment
Treatment Options: 

Photoreceptor transplantation has been tried in 8 patients without improvement in central vision or interruption in the rate of vision loss.  Longer term results are needed.  Resensitizing photoreceptors with halorhodopsin using archaebacterial vectors shows promise in mice.  High doses of vitamin A palmitate slow the rate of vision loss but plasma levels and liver function need to be checked at least annually.  Oral acetazolamide can be helpful in reducing macular edema.

Low vision aids and mobility training can be facilitating for many patients.  Cataract surgery may restore several lines of vision at least temporarily.

Several pharmaceuticals should be avoided, including isotretinoin, sildenafil, and vitamin E. 

References
Article Title: 

Gyrate Atrophy

Clinical Characteristics
Ocular Features: 

Gyrate atrophy is characterized by night blindness, myopia, and multiple round islands of peripheral chorioretinal degeneration which often appear in the first decade of life, sometimes as early as five years of age. Night blindness often begins in late childhood. The atrophic areas slowly progress to the posterior pole and may eventually affect central vision. Both eyes are usually symmetrically affected. All patients have myopia, some with refractive errors ranging up to -20 D. Fluorescein angiography shows hyperfluorescent at the edges of the peripheral atrophy. A zone of pigmentary changes can be seen between normal and atrophic areas.  The electroretinogram may show reduced rod and cone responses with rods affected more than cones in early phases. Dark-adapted ERG documents elevated rod thresholds.  Swollen mitochondria have been described in photoreceptors, corneal epithelium, and in the nonpigmented ciliary epithelium.  Elevated levels of ornithine are found in plasma, urine, spinal fluid and aqueous humor.  Macular edema is commonly present and posterior subcapsular cataracts requiring surgery are common.

Systemic Features: 

Mild muscle weakness may occur due to tubular aggregates in type 2 muscle fibers, which can be visualized with electron microscopy and may lead to loss of these fibers and muscle wasting. Fine, straight hairs have been observed with patches of alopecia. Slow wave background changes on EEG have been described in about one-third of patients and peripheral neuropathy is sometimes a feature.  Hearing loss has been described as well. Some newborns have a temporary elevation of plasma ammonia but once treated usually does not recur.

Genetics

Gyrate atrophy is an autosomal recessive disorder, caused by mutations in the OAT (ornithine aminotransferase) gene on chromosome 10 (10q26).  The enzyme is part of a nuclear-encoded mitochondrial matrix complex.  Many allelic variants have been found.  A large number of affected patients of Finnish origin, most of who share the common L402P mutation, have been described.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

A low protein and especially an arginine-restricted diet have been shown to slow loss of function as measured by ERG and visual field changes.
 

References
Article Title: 
Subscribe to RSS - macular edema