Ординатура / Офтальмология / Английские материалы / The Retina and its Disorders_Besharse, Bok_2011

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antigens, such as anti-recoverin or anti-enolase, while MAR patients may test positive for antibodies directed against bipolar cells.

Prognosis in RP

It is uncommon for a patient with RP to lose all light perception. A study by Grover et al. in 1999 showed that only 0.5% of patients over the age of 45 had no light perception and 50% retained vision better than 20/40. In the typical rod–cone dystrophies, visual loss usually starts in the midperiphery with central visual acuity being spared for many years. Most patients will eventually qualify as being legally blind, often secondary to decreased visual fields prior to being disqualified on the account of decreased central visual acuity. RP is a slowly progressive disease and many patients will eventually experience decreased central acuity, most often from decrease in cone photoreceptor density, macular edema, epiretinal membranes, or retinal pigment defects. However, when there is an unexpected decrease of central acuity, the development of cataracts or cystoid macular edema should be suspected because these sequelae are more amenable to treatment.

Current Treatments

Currently, there is no known cure for most forms of RP, although some treatments have been shown to slow down the progression of the disease and future therapies are promising.

Treatable Forms of RP

A few rare forms of RP are amenable to specific treatments. It is important to rule out these treatable forms of RP because prompt therapy can prevent further damage. The treatable forms of RP include abetalipoproteinemia and adult Refsum disease.

Resources/Support for Patients with RP

The diagnosis of RP can be both frightening and confusing to patients. In addition to having their questions answered by the physician, patients can benefit by meeting with a genetic counselor who can take a detailed family history and answer questions about heritability. Patients should be referred to the many organizations or websites dedicated to providing support for this disease, such as the Foundation Fighting Blindness.

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Optimizing Remaining Vision

It is important that patients with RP have an up-to-date refraction to optimize remaining vision. Patients with significantly decreased visual acuity greatly benefit from a referral to low vision services. A variety of different magnifying devices are available to assist patients with RP. For example, night-vision devices can assist with navigation in dim conditions, although a bright, wide, beam flashlight may be a more cost-effective solution. Various

magnifiers and closed-circuit televisions (CCTVs) are available to enhance reading vision.

Cataractogenesis is frequent in patients with RP. Functional visual improvement can be achieved by cataract surgery in carefully selected individuals with suitable remaining retinal function. The risks of surgery are increased in these individuals who should be counseled specifically regarding the risks of postoperative cystoid macular edema.

Cystoid macular edema in RP has been treated with carbonic anhydrase inhibitors such as oral acetazolamide (Diamox) or topical dorzolamide (Trusopt). These medicines can improve vision in some RP patients with cystoid macular edema; however, their efficacy can decrease with time and many patients cannot tolerate the side effects induced by these medicines.

Vitamin A

Observational studies of patients with RP taking vitamin A and vitamin E supplementation demonstrated a slower decline in cone ERGs than expected and led to a randomized, controlled, double-masked trial, to assess if these supplements could slow down retinal degeneration. Additional subgroup analyses in this study suggested that oral supplementation with 15 000 IU of vitamin A modestly slowed down the loss of ERG amplitude over a 5-year period in certain individuals with RP. Currently, vitamin A supplementation is frequently recommended but its use is not universal. High doses of vitamin A supplementation have also been associated with elevated liver enzymes, elevated triglycerides, and an increased risk of osteoporosis. It seems prudent to check annual liver function tests and triglyceride levels for all patients and bone density scans in older patients taking vitamin A supplementation. Vitamin A should be avoided in children, pregnant women, and those with decreased liver function.

Additionally, from a mechanistic disease perspective, vitamin A should be avoided in forms of RP caused by mutations in the gene ABCA4 due to evidence in animal models of accelerated retinal degeneration. ABCA4 codes for the ABCR protein, which is important for transport of vitamin A-derived all-trans-retinal from the disk to the photoreceptor cytoplasm. Mutations in this gene are responsible for Stargardt macular dystrophy and rarely can also cause autosomal recessive RP.

Docosahexanoic Acid

Docosahexanoic acid (DHA) is an important omega-3 fatty acid that comprises 30–40% of fatty acids in the retina. The exact role of DHA is not known, but it has been proposed to play a role maintaining membrane fluidity, mediating 11-cis retinal transport, and acting as a precursor for neuroprotective factors. Studies in patients with X-linked RP suggested that decreased levels of DHA correlate with decreased ERG responses and have prompted studies to evaluate if supplementation with DHA might slow down retinal degeneration. Two prospective, randomized, double-masked studies (one in patients with X-linked, the other in patients with all forms of RP) failed to show a significant benefit of DHA. However, considering the low risk of adverse effects, many centers do recommend DHA supplementation to patients with RP.

Neuroprotection/CNTF

A relatively new strategy for the treatment of RP is to prevent photoreceptor loss by the delivery of neuroprotective factors. Numerous studies in animal models have documented the successful rescue of photoreceptor degeneration by neurotrophic factors. A delivery system for one of these factors, human ciliary neurotrophic factor (CNTF), has been developed using encapsulated cell technology. These devices use RPE cells that have been transfected to express CNTF and are enclosed by a semipermeable membrane which allows nutrients to diffuse in, but prevents immune attack on the cells. Phase I studies, implanting this device in patients with RP, have been completed without any major adverse events. Phase II studies, which will be able to better assess any visual improvement, are underway.

Gene Therapy

Replacement of defective genes in autosomal recessive forms of RP holds much promise. Currently, three groups

have used an adeno-associated viral vector to deliver normal copies of the all-trans-retinol isomerase (RPE65) in patients with LCA. The treatment has thus far been well tolerated and some patients have demonstrated improvement in subjective vision and to some more objective tests such as pupillary reflexes. Gene therapy holds much promise for treating RP, but several challenges remain. RP and its allied disorders are caused by mutations in over 100 genes. Designing a multitude of vectors for each of these genes poses an arduous challenge.

Autologous RPE Transplantation

Replacement of RPE cells has been attempted using suspensions or sheets of cultured RPE cells or autologous grafts. Engraftment of these injected cells has been demonstrated in animal models. Rescue of photoreceptor degeneration has been achieved suggesting that transplanted RPE cells may modulate photoreceptor death. However, in spite of early photoreceptor rescue in these animal models, long-term restoration of vision has been disappointing.

Stem-Cell-Based Therapies

Cell-based therapy using stem cells is currently being intensely explored for rescuing vision. There are two fundamentally different strategies: one is to limit the progress of photoreceptor loss by introducing cells before such loss has progressed too far; the other is to replace lost photoreceptors. Stem cells are multipotent cells capable of self-renewal and have the potential to develop into many specific cell types. Their capacity for proliferative expansion to a large scale and their ability to produce a number of growth factors make them attractive candidates to be used to replace or repair damaged cells in adult organisms.

Microelectrode Implants

One novel concept for treatment of RP is to bypass the loss of the photoreceptors by electronically stimulating the retina, optic nerve, or visual cortex using microelectrode implants.

Expression of Photosensitive Proteins

A very recent approach for treating RP has been the strategy to bypass photoreceptor loss by using viral vectors to express light-sensitive proteins, such as channel rhodopsin, into postreceptor ganglion cells. Early experiments in small animals have demonstrated successful responses from ganglion cells using this strategy. Much work remains to be done, including how to obtain high

enough expression to provide adequate sensitivity for useful vision.

Conclusions

RP is a significant cause of vision loss in adults and children. Diagnosis is best made by careful history and clinical examination combined with retinal electrophysiology and psychophysical testing. For some individuals, genetic testing can identify causative mutations. While there is currently no cure for RP, many treatment options are emerging and future therapies are promising.

See also: Adaptive Optics; Injury and Repair: Prostheses; Primary Photoreceptor Degenerations: Terminology.

Further Reading

Berson, E. L., Rosner, B., Sandberg, M. A., et al. (1993). A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Archives of Ophthalmology 111: 761–772.

Berson, E. L., Rosner, B., Sandberg, M. A., et al. (2004). Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Archives of Ophthalmology 122: 1297–1305.

Fishman, G. A., Farber, M. D., and Derlacki, D. J. (1988). X-linked retinitis pigmentosa. Profile of clinical findings. Archives of Ophthalmology 106: 369–375.

Grant, C. A. and Berson, E. L. (2001). Treatable forms of retinitis pigmentosa associated with systemic neurological disorders.

International Ophthalmology Clinics 41: 103–110.

Grover, S., Fishman, G. A., Anderson, R. J., et al. (1999). Visual acuity impairment in patients with retinitis pigmentosa at age 45 years or older. Ophthalmology 106: 1780–1785.

Hamel, C. P. (2007). Cone rod dystrophies. Orphanet Journal of Rare Diseases 2: 7.

Hartong, D. T., Berson, E. L., and Dryja, T. P. (2006). Retinitis pigmentosa. Lancet 368: 1795–1809.

Heckenlively, J. R. (1988). Retinitis Pigmentosa. Philadelphia, PA: Lippincott.

Hoffman, D. R., Locke, K. G., Wheaton, D. H., et al. (2004).

A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa. American Journal of Ophthalmology 137: 704–718.

Radu, R. A., Yuan, Q., Hu, J., et al. (2008). Accelerated accumulation of lipofuscin pigments in the RPE of a mouse model for ABCA4mediated retinal dystrophies following vitamin A supplementation.

Investigative Ophthalmology and Visual Science 49: 3821–3829. Sieving, P. A., Caruso, R. C., Tao, W., et al. (2006). Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proceedings of

the National Academy of Sciences of the United States of America

103: 3896–3901.

Weleber, R. G. and Gregory-Evans, K. (2006). Retinitis pigmentosa and allied disorders. In: Ryan, S. J. (ed.) The Retina 395–498. Philadelphia, PA: Elsevier.

Relevant Websites

http://www.ncbi.nlm.nih.gov – Online Mendelian Inheritance in Man (OMIM).

http://www.sph.uth.tmc.edu – Retinal Information Network (Retnet).

Glossary

Allied disorders – Retinitis pigmentosa (RP) is often grouped with a class of more stable, inherited retinal disorders collectively referred to as RP and allied disorders. Some of these allied disorders cause similar clinic findings as RP, e.g., nyctalopia (night blindness), but usually do not show progression and deterioration with time. An example is congenital stationary night blindness (CSNB), which can present with nyctalopia and decreased rod and cone function on the electroretinogram (ERG). Unlike RP, most patients with CSNB have stable visual function. X-linked CSNB is caused by mutations in nyctalopin (NYX) and L-type voltage dependent calcium channel (CACNA1F). Although the majority of mutations of rhodopsin causes typical RP, rare mutations, such as G90D in rhodopsin, produce night blindness with such mild progression late in life that they have been called stationary night blindness. Another allied disorder is achromatopsia, which is caused by mutations in cyclic nucleotide-gated channel subunits (CNGA2, CNGB3) or guanine nucleotide alpha-binding protein 2 (GNAT2). Achromatopsia is associated with severely decreased central and color vision, photophobia, and nystagmus. These symptoms are similar to those that can be seen with some cone–rod dystrophies. Indeed, later in life some modest foveal atrophy can occur and cases of progressive cone–rod dystrophy have been associated with mutations of some of the achromatopsia genes. However, unlike cone–rod dystrophies, which invariably progress, achromatopsia is, in the vast majority of cases, stationary.

Cone dystrophy – Cone photoreceptors are affected and rod photoreceptors are minimally affected or spared in cone dystrophy. Many cases of early cone dystrophies with time will develop significant rod abnormalities.

Cone–rod dystrophy – Cone–rod dystrophy, as a group, involves both photoreceptors with cones affected more than rods. Certain forms of RP present with greater cone than rod involvement on ERG and these patients have been termed to have cone–rod RP. However, in cone–rod dystrophies as a group the primary defect lies in cones and secondaryrod loss

occurs with time. Most investigators consider primary cone–rod dystrophy separate from RP.

Extrinsic factor – An agent external to the organism that contributes to or is causative of a disease state. This can include drugs, foods, normal nutrients (excess or deficiency), toxins, inhaled chemicals, infectious agents, and exposures to radiation such as light, sound, and high-energy particles.

Intrinsic factor – An agent that is inherent to the organism that contributes to or is causative of a disease state.

Mixed intrinsic and extrinsic etiology for a secondary photoreceptor degeneration – This occurs when a person has a genetic variant that creates a toxic metabolite in the presence of an extrinsic molecule that would normally not be encountered.

Mixed model of primary and secondary photoreceptor degeneration – This is considered when a genetic alteration within the photoreceptors is insufficient to cause photoreceptor degeneration by itself, but predisposes to degeneration in the presence of an extrinsic or intrinsic agent. A second mode of combined primary and secondary photoreceptor degeneration is when one group of photoreceptors, such as the rod photoreceptors, undergoes a primary degenerative process that is due to a mutation in a gene that is expressed in those photoreceptors and precipitates apoptosis, which leads to a secondary degenerative process, in this example cones, due to alterations in the cellular environment induced by death of neighboring cells.

Primary retinal degeneration – This occurs when cells in the retina, usually photoreceptors, die secondary to a process that originates within the retina itself. An example of a primary retinal degeneration is RP, which is caused by mutations in genes that encode proteins important for retinal function. A disease can be classified as a primary retinal degeneration if the genetic defect is such that correction of expression of the normal gene product in the photoreceptors is required to correct the abnormality and arrest the degeneration.

Primary retinal degeneration with secondary photoreceptor degeneration – This occurs when photoreceptor degeneration is the result of mutation(s) of a gene that exists in other retinal cells, for

example, retinal pigment epithelial (RPE) cells. Correction of the genetic defect would require modification of the effects of those other retinal cells (e.g, RPE cells).

Retinal atrophy – A broad term encompassing not only processes that occur with retinal degenerations, but also abnormal retinal tissue or cellular loss due to developmental defects and malnutrition.

Retinal degeneration – A process whereby cells in the retina undergo cell death by apoptosis. Most retinal degenerations affect both rod and cone photoreceptors, but some disorders reflect damage that occurs principally in other cell types, e.g., the RPE in Stargardt’s disease and other ABCA4-related retinopathies. Secondary degeneration of the RPE is also common. Transsynaptic degeneration of higherorder cells, bipolar and ganglion cells, can also occur. The general term retinal degeneration should be distinguished from the more specific term, photoreceptor degeneration.

Retinal dystrophy – A broad term that not only encompasses retinal degenerations, but also includes abnormal retinal function due to developmental defects and malnutrition.

Retinitis pigmentosa (RP) – A heterogeneous group of diseases that result in

degeneration of the rod and cone photoreceptors and secondarily the RPE. This degeneration usually leads to a loss of night vision due to the early degeneration of rods, constricted visual fields, decreased responses on ERG, and ultimately a decrease in visual acuity once macular cones begin to degenerate. Typical fundus findings include midperipheral atrophy of the pigment epithelium, bone spicule pigments, retinal vessel attenuation, and waxy pallor of the optic nerve. The term RP usually refers to only rod–cone dystrophies; however, cone–rod dystrophies and cone dystrophies are sometimes grouped under this term. Rod–cone dystrophy – A retinal dystrophy in which the rod photoreceptors are affected more than the cones. Most forms of RP manifest as rod–cone dystrophies.

Secondary photoreceptor degeneration of the extrinsic type – A secondary photoreceptor degeneration of the extrinsic type exists if, despite the underlying molecular defect, one could avoid the photoreceptor degeneration by preventing an individual’s exposure to an extrinsic agent or condition (e.g., toxin, drug, infectious agent, light, and trauma).

Secondary photoreceptor degeneration of the intrinsic type – If one can prevent photoreceptor degeneration by correcting or reversing a systemic or

ocular metabolic or immune process, then it is a secondary photoreceptor degeneration of the intrinsic type.

Histological and Fundus Features of

Retinitis Pigmentosa

The fundus exam in retinitis pigmentosa (RP) reveals midperipheral atrophy of the pigment epithelium, bone spicule pigments greater in the periphery than centrally, retinal vessel attenuation, and waxy pallor of the optic nerve.

Bone Spicule Pigmentation

Bone spicules are intraretinal accumulations of melanin pigment that result from the migration of retinal pigmented epithelial (RPE) cells into the retina after photoreceptor death. These spicules are commonly found in a perivascular pattern and may encircle and occlude these vessels, and are a typical feature of RP. However, there are cases of RP that do not present with bone spicules as well as other disease processes, such as trauma and infection, can result in an appearance that mimics RP by presenting with bone spicules (Figure 1).

Waxy Pallor of the Optic Nerve

Much as the name implies, waxy pallor of the optic nerve refers to the funduscopic appearance of the optic nerve seen in many patients with RP. When retinal photoreceptors die, Mu¨ller cells and astrocytes in the retina undergo gliosis to form scar tissues. It is thought that this process may lead to the waxy pallor of the optic nerve (Figure 2).

Peripapillary/Optic Nerve Head Drusen

Peripapillary drusen/optic nerve drusen are found more commonly in patients with RP. Peripapilliary drusen are histologically different from the drusen found in macular degeneration and are found near or within the optic nerve head. They are thought to result from accumulations of materials in the axons of ganglion cells by axoplasmic stasis and can become calcified with time. Such drusen can cause isolated and asymmetrical visual-field defects, which can be slowly progressive (Figure 3).

Bull’s Eye Maculopathy

A bull’s eye maculopathy results from photoreceptor loss and retinal thinning in a parafoveal distribution. It is often apparent on color fundus photos, but can be visualized on

Figure 1 A fundus photo of a patient with retinitis pigmentosa demonstrating intraretinal pigment accumulations (white arrows), also known as bone spicules, which are a common finding in retinitis pigmentosa. They are caused by the migration of retinal pigment epithelial cells into the retina after photoreceptor degeneration. Modified from Weleber, R. and Evan, K. G. (2006). Retinitis pigmentosa and allied disorders. In: Ryan, S. J. (ed.) The Retina, 4th edn., vol. 1, chap. 17, pp. 395–498. Philadelphia, PA: Elsevier.

Figure 2 An example of the waxy nerve pallor seen in patients with RP. Also note the vascular attenuation and sheathing.

fluorescein angiography as well. Bull’s eye maculopathies are most commonly not only seen in cone–rod dystrophies, but can also be seen in other diseases such as Stargardt’s macular dystrophy, Batten’s disease, and with hydroxychloroquine (Plaquenil) toxicity (Figure 4).

Coats-Like Response

Coats disease is characterized by peripheral retinal telangiectasias, which are dilations of retinal blood vessels, and is usually seen in young males. Rarely, patients with RP can develop localized areas of vascular telangiectasias with exudation similar to those seen in Coats disease. Extravasation of fluid from these vessels can lead to an exudative retinal detachment. This process is termed a Coats-like response (Figure 5).

Classification of RP by Fundus Pattern

Classic Pattern for RP

The classic pattern on fundus exam in RP reveals midperipheral atrophy of the pigment epithelium, bone spicule pigments in the periphery greater than centrally, retinal vessel attenuation, and waxy pallor of the optic nerve (Figure 6).

Inverse RP

The term inverse RP refers to a funduscopic pattern where the central retina exhibits more pigmentary changes and RPE atrophy than the periphery. This term is falling out of favor, as it is now understood that this pattern is often seen with advanced cone and cone–rod dystrophies, as well as some instances of secondary pigmentary retinopathies.

Concentric RP

Concentric RP is a defined by a subgroup of patients who show a consistent pattern of centripetal vision loss from the far periphery toward the center. This distinguishes it from the classic pattern of RP, which starts in the midperiphery and progresses both outward and inward. Histological studies have shown an abrupt transition between diseased and normal areas of retina.

Sector RP

Sector RP is a term that refers to the fundus appearance where abnormal pigmentation and atrophy is confined to only one area of the retina, usually an arc inferior to the macula. Debate exists whether this term is specific for certain gene defects or is a stage in evolution of what will become a more generalized process with time. Autosomal recessive or autosomal dominant regional disease can be characterized by such a sectorial pattern at least in

Figure 4 A fundus photo demonstrating a Bull’s eye maculopathy (dark surrounded by light area).

early disease. The pattern is usually symmetrical between the two eyes. Mutations in rhodopsin (RHO) have been associated with sector RP. These patients are often less symptomatic and their electroretinograms (ERGs) are much less reduced than patients with diffuse or more widespread RP. Early generalized RP can mimic sector RP and, therefore, the diagnosis of sector RP must remain provisional for at least 10 years (Figure 7).

RP Sine Pigmento

The term RP sine pigmento is applied to the early stages of RP where the classical findings of visual-field loss, decreased ERGs, and vascular attenuation may be present, but there is a lack of bone spicules on the fundus exam. This is thought to represent an early manifestation of the disease and most patients will eventually develop bone spicules, although often not until later stages. Another term in use is pauci-pigmentary retinopathy. In the case of patients who develop symptoms later in life and have a normal, or minimally abnormal, fundus appearance, a work-up for autoimmune retinopathy should be considered.

Tapetal-Like Reflex/Sheen

Tapetal-like sheen is a yellowish-white metallic reflex that can be seen in young males with X-linked RP, women who are carriers of this disease, and patients with cone–rod dystrophy. As the disease advances and RPE atrophy progresses, this reflex can fade. This finding is not pathognomonic of RP because it can be seen in other allied disorders (Figure 8).

RP with Preserved Peri-Arteriolar RPE

RP with preserved peri-arteriolar RPE (PPARPE) has been found in families with mutations in the crumbs

homolog 1 gene (CRB1). These patients present with the typical findings of RP, but for reasons not understood, have preservation of the RPE near arterioles.

Pigmented Paravenous Retinochoroidal

Atrophy

In pigmented paravenous retinochoroidal atrophy (PPRCA), degeneration and accumulation of bone spicules are limited to the areas around the retinal veins. These patients are often asymptomatic, but with careful testing, scotomas corresponding to the areas of degeneration can be identified. Typically, the ERG is minimally reduced and disease is thought to be, at most, slowly progressive. Although PPRCA has been thought not to be inherited, mutations in the CRB1 gene have been found in families demonstrating dominant inheritance (Figure 9).

Figure 6 Fundus photo of a typical patient with RP. Note the pallor of the optic nerve, the vascular attenuation, atrophy of the pigment epithelium, and bone-spicules. Reproduced from Weleber, R. G., Butler, N. S., Murphey, W. H., Sheffield, V. C., and Stone, E. M. (1997). X-linked retinitis pigmentosa associated with a two base-pair insertion in codon 99 of the RP3 gene RPGR.

Archives of Ophthalmology 115: 1429–1435.

Fundus Albipunctata

Fundus albipunctata is an autosomal recessive disease that does not result in a retinal degeneration like RP, but can cause a congenital stationary night blindness. It is more accurately classified as an allied disorder. It is caused by mutations in the retinol dehydrogenase 5 gene (RDH5), which results in problems regenerating visual pigment. As a result, these patients have severely decreased rod recovery with prolonged dark adaptation. The fundus exam shows many discrete yellowish-white dots at the level of the RPE. Atrophic lesions in the macula can occur in many patients in later years (Figure 10).

Retinitis Punctata Albescens

Retinitis punctata albescens is an autosomal recessive disease caused by mutations in the retinaldehyde-binding protein 1 gene (RLBP1). Similar to fundus albipunctata, this disease presents with severe night blindness and small, discrete, yellowish-white lesions in the fundus, but can have a pigmentary retinopathy as well. Later stages of RPA may develop diffuse disease similar to advanced RP.

Gyrate Atrophy

Gyrate atrophy is an autosomal recessive form of diffuse choroidal atrophy caused by mutations of the gene (OAT ) for ornithine-@-aminotransferase (OAT). The deficiency of this enzyme results in elevated plasma and tissue levels of ornithine, which exert a cytotoxic effect on the RPE, possibly by endpoint inhibition of a common intermediate for proline synthesis, L-D1-pyrroline-5-carboxylic acid (P5C), which is normally formed from ornithine by OAT and from glutamic acid by P5C synthase. The early stage of gyrate atrophy is associated with sharply demarcated areas of peripheral chorioretinal atrophy. Later stages develop more diffuse and generalized total vascular choroidal atrophy. Dietary restriction of arginine, the precursor for ornithine, can be beneficial. Additionally, a rare subset of patients has been shown to respond with lowered

Figure 8 An example of tapetal-retinal sheen seen in a carrier of X-linked retinitis pigmentosa.

Figure 9 Example of pigmented paravenous retinal choroidal atrophy.

ornithine levels to treatment with vitamin B6 (pyridoxine HCL), which acts as a co-factor for the defective enzyme. Disorders such as gyrate atrophy blur the distinction between primary and secondary retinal degenerations leading to the realization that it is difficult to draw the line between RP and allied diseases (Figure 11).

Choroideremia

Choroideremia is an X-linked disease, which is caused by a mutation in the CHM gene and leads to progressive degeneration of the retina, RPE, and choroid. The CHM gene encodes the homolog of the Rab escort protein 1 (REP1) which is thought to be important in the function of a Rab geranylgeranyl transferase. Choroideremia can often be mistaken for X-linked RP, as the two diseases can share several features including: nyctalopia, retinal RPE atrophy, pigmentary changes, and decreased ERGs and X-linked inheritance. Unlike the waxy nerve pallor seen in RP, patients with choroideremia will often have a normal-appearing nerve and relative preservation of the macula and peripapillary retina (Figure 12).

Syndromic Forms of RP

Abetalipoproteinemia

Also known as Bassen–Kornzweig syndrome, abetalipoproteinemia results from a deficiency of beta lipoproteins, which are necessary for normal absorption of fat-soluble vitamins from the gut, leading to poor absorption of vitamins A, D, E, and K. The syndrome is characterized by low levels of fat-soluble vitamins, ataxia, acanthocytosis,

Figure 10 A fundus photograph of fundus albipunctata. Note the characteristic punctate white dots.

Figure 11 Gyrate atrophy. Note the scalloped peripheral areas of chorioretinal degeneration as well as central atrophy.