Retinitis Pigmentosa

Early loss of central vision REF: khurana 4th ed p. 260-262

Retinitis pigmentosa

• Night blindness is earliest feature
• Defective dark adaptation
• Partial or ring scotoma
• Tubular vision
• Loss of central vision by age of 50-60 years
• Fundus changes

(a) Retinal pigmentary changes typically perivascular and resemble bone corpuscles in shape

(b)Attenuated or narrowed retinal arterioles

(c) Pale and waxy optic discs

• Marfan syndrome is characterised by
• Skeletal changes – Long extremities, arachnodactly (spider fingers)
• Ectopia lentis – Dislocation of lenses upwards & temporally
• Aortic aneurysm
• Systemic conditions associated with retinitis pigmentosa (RP)-

a.Laurence-Moon-Biedl syndrome – most commonly associated & characterised by RP, obesity, hypogonadism, polydactyly & mental defect.

b. Usher’s syndrome: RP & labyrinthine deafness

c.Bussen-Kornzweig disease (Abetalipoproteinemia) : RP, fat malabsorption, spinocerebellar degeneration, and acanthocytosis

d.Kearns-Sayer syndrome: Mitochondria] myopathy characterised by external ophthalmoplegia, lid ptosis, cardiac conduction block & mild RP.

e.Cockayne’s syndrome: RP, progressive infantile deafness, dwarfism, mental retardation, nystagmus & ataxia.

f.Refsum’s syndrome: RP, peripheral neuropathy cerebellar ataxia.

g.Hallgren’s syndrome: RP, vestibulo-cerebellar ataxia, congenital deafness & mental deficiency

In retinitis pigmentosa rods are involved first followed by cones. As the disease progresses there is loss of night vision and peripheral field of vision. Only in the later stages of the disese there is loss of central vision.

Retinitis Pigmentosa is a group of hereditary retinal degenerative disorder characterized by progressive dysfunction of photoreceptors, associated with progressive cell loss and atrophy of several retinal layers. 

Hallmark symptoms are: night blindness, progressive loss of peripheral field of vision and coalescing ring scotomas.

Characteristic fundoscopic findings are: attenuated retinal arterioles, waxy pale optic disc, mottling of retinal pigment epithelium, and peripheral retinal pigment clumping (bone spicule formation). ERG shows reduced/absent retinal function. EOG lacks usual light rise.

Some forms of retinitis pigmentosa occur in association with rare, hereditary systemic diseases like olivopontocerebellar degeneration, Bassen-Kornzweig disease (abetalipoproteinemia), Kearns-Sayre syndrome, Refsum’s disease, and neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome.

• Chronic treatment with chloroquine, hydroxychloroquine, and phenothiazines (especially thioridazine) can produce visual loss from a toxic retinopathy that resembles retinitis pigmentosa.
• Hallervorden-Spatz disease or neurodegeneration with brain iron accumulation 1 (NBIA1) or pantothenate kinase-associated neurodegeneration (PKAN), is characterized by extrapyramidal and cognitive abnormalities, dysarthria, dysphagia, and ocular abnormalities (eg, gaze palsies, optic atrophy).

Ref: Horton J.C. (2012). Chapter 28. Disorders of the Eye. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

Retinitis Pigmentosa:

It is a group of heterogeneous hereditary rod-cone dystrophies characterized by progressive dysfunction of the photoreceptors, associated with progressive cell loss and eventual atrophy of retinal layers.

It occurs sporadically or in an autosomal recessive, dominant, or X-linked pattern.
Hallmark symptoms are night blindness (nyctalopia) and gradually progressive peripheral visual field loss as a result of increasing and coalescing ring scotomas.

Most characteristic fundoscopic findings:

• Attenuated retinal arterioles
• Waxy pale optic disk
• Mottling of the retinal pigment epithelium
• Peripheral retinal pigment clumping, referred to as “bone-spicule formation”

Ref: Fletcher E.C., Chong N., Augsburger J.J., Corrêa Z.M. (2011). Chapter 10. Retina. In P. Riordan-Eva, E.T. Cunningham, Jr. (Eds), Vaughan & Asbury’s General Ophthalmology, 18e.

Retinitis pigmentosa is a familial degenerative disease of the retina that most often has recessive genetics. The initial problem appears to be alterations in the pigmented epithelium below the retina, particularly in the most anterior portions of the retina. The pigmented epithelial cells become disrupted and leak pigment, which accumulates along the attenuated blood vessels (and can be seen with an ophthalmoscope). A consequence of this damage is that the rod cells that are normally nutritionally supported and “groomed” by the pigment epithelium also undergo degenerative changes. Since the cones are relatively preserved, day vision is preserved, but night vision, which is highly dependent on rods, begins to decay. With disease progression, vision is completely or nearly completely lost and the retina becomes so distorted that only a single row of cone nuclei with scattered stumpy cone remnants is all that remains of the photoreceptor layer.

Ref: Fletcher E.C., Chong N., Augsburger J.J., Corrêa Z.M. (2011). Chapter 10. Retina. In P. Riordan-Eva, E.T. Cunningham, Jr. (Eds), Vaughan & Asbury’s General Ophthalmology, 18e.

Retinitis pigmentosa is a group of heterogeneous hereditary retinal degenerations characterized by progressive dysfunction of the photoreceptors, associated with progressive cell loss and eventual atrophy of several retinal layers. Inheritance of the typical form can be autosomal recessive, autosomal dominant, or X-linked recessive.

Ans. is ‘b’ i.e., Refsum’s syndrome

Refsum disease is characterized by ataxia, ichthyosis, cardiomyopathy, retinitis pigmentosa and absent tendon reflexes.

C i.e. Retinitis pigmentosa

            B i.e. Hallervordm spatz syndrome

B i.e. Early diagnosis & treatment prevents progression

–  Retinitis pigmentosa may be associated with Usher’s syndrome, NARP (= Neuropathy, Ataxia, RP) syndrome, Bassen Karzweig syndrome (a beta lipoproteinaemia = deficiency of Beta lipoproteins), Friedreich’s ataxia, Bardet Biedl syndrome, Cockayne’s syndrome, Refsum disease (phytanic acid alpha hydrolase deficiency), Kearns-Sayre syndrome, and HaXgren’s syndrome.

Mn-“Use No Basse (1141) Fried Cock Bird Relief (Fight) in Shared Hall”

Retinitis pigmentosa is a b/1 progressive degenerative disease of rods & cones beginning in childhood & resulting in blindness in middle or advanced age. No treatment is effective in preventing progression(2. It may be sporadic, AD or X-linked with visual acuity not dimishine till late in courseQ.

Pigmentary Retinal Dystrophy/ Retinitis Pigmentosa (R.P.)

RP encompasses clinically and genetically diverse group of diffuse retinal dystrophies that affect the photoreceptors (rodes more than cones) and retinal pigment epithelium (RPE), involving entire fundus. Although initial geographical involvement begin either in periphery or macula. Death of rod photoreceptors impaired vision in dim light, cause tunnel vision and prolonged dark adaptation.

This primary pigmentary retinal dystrophy is hereditary disorder affecting rodes more than cones and characterized by night blindness, tubular vision, annular (ring) scotoma bony spicule pigmentation, arteriolar attenuation and waxy pallor of optic discQ

Etiology

Many cases are d/t mutation of pro-23-his rhodopsin gene. RP may occur as isolated sporadic disorder, or be inherited in an autosomal dominant (AD has best prognosis) > X-linked usually recessive (least common but most severe. Female carriers may have normal fundi or exhibit a golden metallic tapetal reflex temporal to the macula & atrophic & pigmentary peripheral irregularities).

– Male:Female = 3:2

Associated Syndromes

1. Bassen Karzweig Syndrome (AR)Q is d/t deficiency of betalipoproteinQ resulting in intestinal malabsorption (jejunal biopsy is diagnostic) + RP, ataxia (spinocerebellar) & acanthocytosis. Treatment is vitamin E

2. Refsum Disease is an AR deficiency of enzyme phytanic acid 2 hydroxylaseQ resulting in accumulation of phytanic acid + polyneuropathy, cerebellar ataxia, deafness, anosmia, cardiomyopathy, icthyosis & elevated CSF protein in the absence of pleocytosis (cytoalbuminous inversion) + RP with salt pepper changes.

Usher’s Syndrome (AR)Q is RP & sensoryneural labrynthine deafness

4. Kearns- Sayre syndrome Q is mitochondrial cytopathy (d/t mitochondria DNA deletion) characterized by atypical RP (coarse pigment clumping in central fundus) with chronic progressive ophthalmoplegia (ocular myopathy eg. ptosis) & heart block..

5. Bardet-Biedl/Laurence Moon Biedl Syndrome (ARQ) is characterized by RP, obesity, hypogenitalism, polydactyly and mental retardationQ.

6. Cockayne’s Syndrome is RP dwarfism, deafness, mental retardation, nystagmus, ataxia, bird like facies, premature aging & flexion contracture of limbs.

1. Hallgren’s syndrome is RP, deafness, cerebello­vestibular ataxia & mental retardation.
2. Friedreich’s ataxia is RP, posterior column disease, ataxia, nystagmus & subaortic stenosis.

9. NARP (Neuropathy, Ataxia and RD syndrome

Treatment

No treatment is effectiveQ. Vitamin A may be useful.

X-linked usually recessive (least common but most severe. Female carriers may have normal fundi or exhibit a golden metallic tapetal reflex temporal to the macula & atrophic & pigmentary peripheral irregularities). – Male:Female = 3:2 Associated Syndromes 1. Bassen Karzweig Syndrome (AR)Q is d/t deficiency of betalipoproteinQ resulting in intestinal malabsorption (jejunal biopsy is diagnostic) + RP, ataxia (spinocerebellar) & acanthocytosis. Treatment is vitamin E 2. Refsum Disease is an AR deficiency of enzyme phytanic acid 2 hydroxylaseQ resulting in accumulation of phytanic acid + polyneuropathy, cerebellar ataxia, deafness, anosmia, cardiomyopathy, icthyosis & elevated CSF protein in the absence of pleocytosis (cytoalbuminous inversion) + RP with salt pepper changes. 3. Usher’s Syndrome (AR)Q is RP & sensoryneural labrynthine deafness 4. Kearns- Sayre syndrome Q is mitochondrial cytopathy (d/t mitochondria DNA deletion) characterized by atypical RP (coarse pigment clumping in central fundus) with chronic progressive ophthalmoplegia (ocular myopathy eg. ptosis) & heart block.. 5. Bardet-Biedl/Laurence Moon Biedl Syndrome (ARQ) is characterized by RP, obesity, hypogenitalism, polydactyly and mental retardationQ. 6. Cockayne’s Syndrome is RP dwarfism, deafness, mental retardation, nystagmus, ataxia, bird like facies, premature aging & flexion contracture of limbs. 7. Hallgren’s syndrome is RP, deafness, cerebello-vestibular ataxia & mental retardation. 8. Friedreich’s ataxia is RP, posterior column disease, ataxia, nystagmus & subaortic stenosis. 9. NARP (Neuropathy, Ataxia and RD syndrome Treatment No treatment is effectiveQ. Vitamin A may be useful. ” v:shapes=”_x0000_s1027″>Clinical Features

– Diagnostic criteria for RP include bilateral involvement (mostly) with loss of peripheral and night vision along with classical tried of RP (1) arteriolar attenuation (2) retinal bone spicule pigmentation and (3) waxy disc pallor

– Nyctalopia (night blindness) i.e. impaired vision in dim light is earliest feature, most commonly seen in young adults (2^nd – 3^,d decade).

– Prolonged (defective) dark adaptation i.e. slowed adaptation to decreased (or even increased) lighting. Patients have problem in dimly lit theaters, restaurants and when they come indoors from bright sun light

– Visual field constriction i.e. slowly progressive loss of peripheral vision or concentric contraction of visual field results in characteristic tubular (tunnel) vision. It occurs in midstage of disease and there is poor correlation between acuity and extent of tunnel vision. Patient may appear clumsy & colloid with objects b/ o unrecognized tunnel vision.

– Ultimately central vision is also lost by 50-60 years of age. Later manifestations (complications) include posterior sub capsular cataract (in middle age), cystoids macular edema. Both reduce central acuity even when the RP affects the peripheral retina only. Choroidal bodies (sclerosis), progressive chorioretinal atrophy and epiretinal membrane may be other latge complications

Fundus Examination

– Classical key features include atrophy and thinning of RPE, narrowing (attenuation) of retinal arterioles and bone spicule intraretinal pigmentary changes (typically perivascular and resembling bone corpuscles). These changes are initially found in mid peripheral (equatorial) regions f/b far peripheral retina with relative preservation of macula.

– There is gradual increase in density with anterior and posterior spread, resulting in tessellated fundus appearance (d/t RPE atrophy) and unmasking of choroidal vessels.

– Gliotic waxy nerve pallor of optic disc (waxy pale optic disc) from reactive gliosis, macular atrophy, epiretinal membrane & CMG are late features.

Perimetry

– Small mid peripheral scoloma (earliest) that gradually coalesce to form the classical annular or ring scotoma (complete or partial), which expands both peripherally & centrally. It leaves tiny central island of vision which may eventually be lost.

– Useful in monitoring progression of disease

Dark Adaptometry

–  Prolonged dark adaptation is useful for diagnosing early uncertain cases

ERG

–  In early RP, scotopic rod and combined response is reduced (i.e. ERG is subnormal)

Gradually photopic response becomes reduced and eventually ERG is extinguished

EOG

–  Markedly subnormal with absence of light rise (peak)

– Retinitis pigmentosa sine pigmento is characterized by all clinical features except there is no visible pigmentary changes in the fundus

–    Retinitis punctata albescens is characterized by multiple scattered white dots
mostly between posterior pole & equator. Other findings are same to R.P.

Sectorial R.P. Involvement of only one quadrant (usually nasal) of the fundus – Pericentric R.P. All features are similar except that pigmentary changes are confined to an area, immediately around the macula.

A i.e. Ring scotoma

D i.e. ERG normal

–  Typical retinitis pigmentosa/primary pigmentary retinal dystrophy is hereditary disorder affecting rodes more than cones and characterized by night blindness, tubular vision, annular (ring) scotoma bony spicule pigmentation, arteriolar attenuation and waxy pallor of optic discQ.

– In Retinitis pigmentosa, “the symptoms are characteristic, the most prominnent being defecive vision in the dusk (night blindness, nyctalopiaQ). But there’s no such option given here. Diplopia is not seen in RP, and central scotoma is very late feature. Peripheral field contraction is an early finding on perimetry, but definitely Ring scotoma is a more chacteristic feature and a relatively early one too. So, its best to go with “Ring scotoma” as the answer here.

Electroretinogram indicates the activity of retina (especially rods and cones) and is subnormal or abnormal in diseases of retina e.g. retinitis pigmentosaQ. ERG has no role in assessing the functional integrity of optic nerve and so it can’t be abnormal in optic neuritisQ.

Causes of

Ans. Less sensitive than the EOG

Ans. Retinitis pigmentosa

Ans. Autosomal recessive

Ans. Primary angle closure glaucoma

Ans. Lowe’s syndrome

Ans. Retinitis of Roth

Ans. Retinal haemorrhages

Ans. Retinitis pigmentosa

Ans. Hallervorden Spatz Syndrome

Ans. Retinitis pigmentosa

Ans. D i.e. All of the above

Cataract

• Systemic causes of cataract:

– HTN,

– Smoking,

– DM

MC cataract in adults: Cortical cataract

• Complicated cataract: Characteristic sign is polychromatic lusture
• Lamellar cataract: Associated with

– Malnutrition &

– Hypoparathyroidism

• After cataract: Nd: YAG LASER capsulotomy is done

Ans. A: Prominent retinal vessels

Autosomal dominant is benign and is symptomatic only in adult life. X-linked recessive is least common. It is also a very severe form.

Degeneration of rods commences near the equator. Macular region is not affected until late in the disease.

The symptoms of retinitis pigmentosa are characteristic, the most prominent being defective vision in the dusk (night blindness/nyctalopia). It is due to degeneration of rods, which are primarily responsible for vision in low illumination. The visual field show concentric reduction. In early cases a partial or complete annular/ring scotoma is found. As the disease progresses the field becomes gradually smaller until at last it is reduced to a restricted area around the fixation point (tubular vision).Hence person has difficulty in moving about.

Initially the equatorial region is affected. Ophthalmoscopic findings in the affected zones shows the retina studded with small, jet black spots resembling bone corpuscles with a spidery outline. The retinal pigment epithelium becomes transparent so that the choroid vessels become visible and the fundus appears tessellated or tigroid.

The retinal veins, never the arteries, often have a sheath of pigment for part of their course.

The retinal vessels becomes extremely attenuated and thread like.

The disc exhibits the characteristics of primary optic atrophy. It is pale and have a wax like yellowish appearance and is often termed as ‘consecutive optic atrophy’ (Ganglion cells destroyed with degeneration of the axial cylinders and optic nerve is known as consecutive atrophy).

Ocular associations of retinitis pigmentosa are myopia, chronic simple glaucoma.

Systemic associations of retinitis pigmentosa are in the form of various syndromes:

• Laurence – Moon – Biedl syndrome – obesity, hypogonadism, polydactyly and mental retardation.
• Usher’s syndrome – deaf mutism.

Secondary retinitis pigmentosa due to infections like syphilis, mumps, German measles (rubella) and due to drug like chloroquine must be differentiated from primary retinitis pigmentosa.

Treatment: is unsatisfactory

• Vasodilators – nicotinic acid.
• High doses of Vitamin A.

Ans. B i.e. Central scotoma

Retinitis pigmentosa

• Feature: Loss of visual acuity
• Microscopy: Irregular black deposits of clumped pigment in the peripheral retina (Bone spicules)

Ans. B i.e. Retinitis pigmentosa

Ans. C: Retinitis pigmentosa

Ans. A: Retinitis pigmentosa

GIT premalignant conditions

• Of the four major primary small-bowel tumors (adenocarcinomas, lymphomas, carcinoid, and leiomyosarcomas), adenocarcinomas and lymphomas are associated with diseases that seem to increase the risk of developing these malignancies.
• Immunoproliferative small intestinal disease and celiac disease, are thought to predispose patients to the development of primary lymphoma.
• Increased risk is also associated with conditions, such as immunodeficiency syndromes, nodular lymphoid hyperplasia, Crohn’s disease, the gastrointestinal polyposis syndromes, hereditary nonpolyposis colon cancer, neurofibromatosis, long-standing ileostomy, and urinary diversion procedures.
• Patient with long standing ulcerative colitis are at risk of developing colonic epithelial dysplaia and carcinoma.
• Oral cavity premalignant conditions
• Many oral SCCs develop from premalignant conditions of the oral cavity.
• A wide array of conditions have been implicated in the development of oral cancer, including leukoplakia, erythroplakia, palatal lesion of reverse cigar smoking, oral lichen planus, oral submucous fibrosis, discoid lupus erythematosus, and hereditary disorders such as dyskeratosis congenital and epidermolysis bullosa
• Other pre-malignant conditions include actinic keratosis, Barrett’s esophagus and cervical dysplasia.

Ans. is ‘b’ i.e., Jet- black spots with pale-waxy disc

Examination findings in retinitis pigmentosa

Ophthalmoscopic findings are characteristic and include :-

1. Retinal pigmentary changes (Bone spicule intraneural retinal pigmentation) : – Retina studded with small, jet-black spots resembling bone corpuscles with a spidery outline. These pigmentary changes are typically perivascular and retinal veins (never arteries) have a sheath of pigment for part of their course. These changes affect equatorial region initially sparing the posterior pole and periphery. Later in the course of disease whole retina is involved.
2. Attenuated and thread like retinal arterioles and veins.
3. Pale and waxy optic disc (consecutive optic atrophy).
4. Thinning and atrophy of retinal pigment epithelium (RPE) in mid and far peripheral retina with relative sparing of RPE at macula.

Electroretinogram (ERG) and particularly the electro-oculogram (EOG) are markedly subnormal.

Ans. is ‘a’ i.e., Retinitis pigmentosa

Associations of retinitis pigmentosa

Ocular associations : These include myopia, primary open angle glaucoma, microphthalmos, conical cornea and posterior subcapsular cataract.

Systemic associations : These are in the form of following syndromes :-

i) Laurence-Moon-Biedl syndrome : It is characterised by retinitis pigmentosa, obesity, hypogenitalism, polydactyly and mental deficiency.

ii) Cockayne’s syndrome : It comprises retinitis pigmentosa, progressive infantile deafness, dwarfism, mental retardation, nystagmus and ataxia.

iii) Refsum’s syndrome : It is characterized by retinitis pigmentosa, peripheral neuropathy and cerebellar ataxia.

iv) Usher’s syndrome : It includes retinitis pigmentosa and labyrinthine deafness.

v) Hallgren’s syndrome : It comprises retinitis pigmentosa, vestibulo-cerebellar ataxia, congenital deafness and mental deficiency.

Ans. is ‘a’ i.e., Retinitis pigmentosa

Retinal pigmentary changes (Bone spicule intraneural retinal pigmentation) : – Retina studded with small, jet-black spots
resembling bone corpuscles with a spidery outline. These pigmentary changes are typically perivascular and retinal veins
(never arteries) have a sheath of pigment for part oftheir course. These changes afrect equatorial region initially sparingthe
posterior pole and periphery. Later in the course ofdisease whole retina is involved.