Retinitis pigmentosa is a group of hereditary retinal diseases characterized by progressive degeneration of photoreceptors. It begins with night blindness and peripheral vision loss and can progress to tunnel vision or legal blindness. Genetic mutations affecting photoreceptor structure and function or RNA splicing are responsible. On examination, bone spicule pigmentation, vascular attenuation, optic nerve pallor and RPE changes are seen. Diagnosis is confirmed by electroretinography showing photoreceptor dysfunction. There is currently no cure but management focuses on low vision aids, vitamins, and gene or stem cell therapies which are under investigation.

1. Dr.P.Neha kamalini,
M.S.Ophthalmology

2.  The term retinitis pigmentosa (RP) encompasses a set of
diverse hereditary disorders, that affect the photoreceptors and
retinal pigment epithelium(RPE), diffusely across the entire
fundus but begin with initial geographic involvement in either
the periphery or the macula.
 It is the most common hereditary fundus dystrophy.

3. HISTORY
 The first description of the fundus findings and the use of the
term “retinitis pigmentosa” are attributed to Donders in 1855
and 1857
Terminology
 primary pigmentary degeneration
 rod-cone dystrophy
 tapetoretinal degeneration.

4. Incidence
 The world wide incidence is 1:5000.
 Age: It appears in the childhood and progresses slowly, often
resulting in blindness in advanced middle age.
 Race: No race is known to be exempt or prone to it.
 Sex: Males > females in a ratio of 3:2.
 Laterality: Disease is almost invariably bilateral and both the eyes
are equally affected.

5. Genetics in RP:
RP may occur as
1. Sporadic (simplex) disorder
2. Inherited disorder
 Autosomal recessive (25%)
 Autosomal dominant (25%)
 X-linked recessive (10%) – most severe.

6. Rhodopsin mutations (chromosome 3q21):
 Rhodopsin is the protein responsible for initiating the cascade
of phototransduction.
 At least 100 mutations have been reported in the rhodopsin
gene associated with autosomal dominant and recessive RP.

7. Peripherin/RDS mutations (chromosome 6p12):
 Peripherin/RDS protein is involved in the structural integrity
of photoreceptor.
 Nearly 39 mutations identified in this gene have been seen to
be associated with autosomal dominant RP and macular
dystrophy.

8. Abnormal pre-mRNA splicing:
 Several genes with mutations found in RP patients, such as
PRPF8 (chromosome 17p13.3), PRPF31(chromosome
19q13.4), and PRPF3 (chromosome 1q21.1) have a role in the
RNA splicing.
Others:
 mutations in RP GTPase regulator
 mutations in ABCR gene.

9. Night blindness (nyctalopia):
 It is the characteristic feature and may present several years
before the visible changes in the retina appear.
 It occurs due to degeneration of the rods.
 The usual age of onset of night blindness is
10.7 years for autosomal recessive disease
23.4 years for autosomal dominant disease

10.  Massof and Finkenstein have characterized RP into two types:
Type 1 RP
 childhood onset night blindness
 early loss of rod sensitivity compared to cone sensitivity
Type 2 RP
 adult onset night blindness
 combined loss of rod and cone sensitivity.

11. Dark adaptation
 Light threshold of the peripheral retina is increased; though
the process of dark adaptation itself is not affected until very
late.
Visual field loss:
 In general there is progressive loss of peripheral vision.
 However, most patients become symptomatic only when
significant peripheral field has been lost and the field loss
reaches the stage of ‘tunnel vision’.

12. Fundus changes
1.‘Bone-spicule’ intra retinal pigment:
 Intraretinal, bone spicule pigment formations represent migration of
pigment into the retina from disintegration of RPE cells with
accumulation in the interstitial spaces surrounding retinal vessels.
 These are typically perivascular
 Initially, these changes are found in the equatorial region and later
spread both anteriorly and posteriorly.

14. 2. Gliotic ‘waxy pallor’ of the optic nerve head.

15.  A “golden ring” or yellowish-white halo can often be seen
surrounding the optic disc in early RP
 As disease progresses, this golden ring is replaced with
peripapillary mottling, hyperpigmentation, and atrophy of the
RPE
 The optic nerve head cup-to-disc ratio has been reported to be
significantly smaller in RP patients of all types (0.19
compared to 0.35 in normal subjects)
 Optic disc drusen occur more frequently in patients with RP.

16. Peripapillary chorioretinal pallor, or the “golden ring”
sign, characteristic of early retinitis pigmentosa

17. 3. Attenuation of retinal arterioles.
4. Thinning and atrophy of the RPE in the mid- and far-
peripheral retina.
5. Relative preservation of the RPE in the macula.

19.  Severe peripheral pigmentation with marked arteriolar
narrowing

20. Female carriers of the XLR form
 may have normal fundus or
 show a golden-metallic (‘tapetal’) reflex at the macula and/or
 small peripheral patches of bone spicule pigmentation.

21. Tapetal reflex at the macula

22. small peripheral patches of bone spicule
pigmentation.
Tapetal reflex at the macula

23. Vitreous abnormalities
 The most common abnormality of the vitreous in RP is the
presence of fine, dust-like pigmented cells released from
degeneration of the RPE.

24. Anterior-segment abnormalities
 posterior subcapsular cataract (common in all forms of RP)
 open-angle glaucoma (3%),
 keratoconus (uncommon)

25. Photopsia
 Many patients with RP at some time during the course of their
disease have light flashes.
 These photopsias are described as tiny, blinking or shimmering
lights.
 The phenomenon is similar to that reported by patients with
ophthalmic migraine except that,
• the photopsias are generally stationary within the field.
• the photopsias may be continuous rather than episodic.
 As the scotomas become denser over the years, the photopsias
decrease and finally disappear.

26. Other features
 The macula may show atrophy, epiretinal membrane (ERM)
formation and cystoid macular oedema (CMO).
 cystoid macular edema is seen because the efficiency with
which fluid is pumped across the RPE is compromised or
because of slow retinal vascular leakage
 Myopia is common.

27. Investigations
 Electroretinography
 Visual Field Testing
 Dark Adaptation Testing
 Color Vision Tests
 Fluorescein Angiography
 Fundus Autofluorescence
 Optical Coherence Tomography
 Electro-Oculography
 Multifocal Electroretinography
 Visual Evoked Cortical Potential
 Genetic Testing

28. Electroretinography
 The full-field (Ganzfeld) electroretinogram (ERG) is sensitive
to even mild photoreceptor impairment.
 Rod b-wave amplitudes are reduced in the earliest stages of
disease, when the retina may appear clinically normal and
vision complaints are minimal.

29. ERG is repeated every 1 – 2 years for :
 Confirmation of the diagnosis.
 Determination of the rate of progression.
 Monitoring the effects of therapy, such as vitamin A
administration or other.

30. Visual Field Testing
 Goldmann perimetry is preferable for retinitis pigmentosa
visual field testing
 Even moderate stages of rod disease typically show extensive
peripheral field loss to the small, I4e Goldmann target,
whereas cone-rod disease leaves peripheral fields more intact.
 Two color scotopic perimetry has been developed by Ernst et
al using light emitting diodes of two wavelengths (530 and
660 nm) that permit testing of each location for rod and cone
sensitivities.

31. Dark Adaptation Testing
 One of the instruments to do this is the Goldmann-Weekers dark
adaptometer.
1.The patient is placed in darkness and asked to detect the dimmest
possible (threshold) light, which becomes progressively dimmer
as time proceeds.
 Final absolute threshold sensitivity is normally reached after 30–40
minutes in the dark.
2. An alternative test strategy is to determine only the final thresholds
after 45–60 minutes in the dark.
 Thresholds are tested in several different retinal locations to sample
the distribution of disease.

32. Color Vision Tests
 Retinitis pigmentosa patients rarely volunteer problems with color vision
because nearly all can readily differentiate the major colors of red, green,
and blue
 In rod-cone dystrophies:
tritan (‘blue-yellow’) color discrimination loss on the Farnsworth
indicates acuity loss within the next few years.
 In cone dystrophies:
loss of color discrimination normally parallels visual acuity loss.
 The Ishihara and American Optical color plates were designed specifically
to detect congenital red-green abnormal individuals and are less useful than
the D-15 test for the evaluation of early macular dysfunction that results
from a retinal dystrophy.

33. Fundus Autofluorescence
 Lack of signal on FAF - areas of RPE atrophy
 areas of increased FAF - areas with persistent macular edema ,
areas of surviving retina.
 Most RP patients demonstrate a perifoveal ring of increased
autofluorescence within the macula, which denotes the border
between functional and dysfunctional retina

34. central ring of hyperfluorescence
mottled hypofluorescence in the region along the arcades.

35. Optical Coherence Tomography
 OCT abnormalities range from reduction in retinal thickness
due to photoreceptor loss, to increase in retinal thickness due
to macular edema.

36. Spectral-domain optical coherence tomography of a patient with retinitis
pigmentosa without cystoid macular edema and with cystoid macular
edema

37. Electro-Oculography
 Electro-oculography (EOG) is abnormal whenever the ERG is
abnormal
 and thus provides useful information only when the ERG is
normal.
 Therefore, EOG is not performed automatically with every
ERG examination.

38. Multifocal Electroretinography
the multifocal ERG (mfERG) is a localized response elicited
by simultaneous stimulation of multiple discrete areas of the
central retina.
 The local responses may be extracted by correlating the
recorded response with the stimulus sequence
 In a diffuse retinal disease such as retinitis pigmentosa, the
Ganzfeld ERG is a more useful overall estimator of retinal
function
 However, the mfERG can be used to explore local aspects of
cone function.

39. Diagnostically it is perhaps most useful in the determination of
 chloroquine and hydroxychloroquine toxic maculopathies
 occult maculopathy
 for the differentiation of macular versus optic nerve related
central scotomas

40. Visual Evoked Cortical Potential
 Visual evoked cortical potential (VECP) monitors visual
signals that reach the cortex and is dominated heavily by
macular function, with a far smaller contribution from the
peripheral retina.
 Any disturbance of retinal function, altered optic nerve
conduction, or visual cortex processing alters the VECP.

41. Genetic Testing
 new advances in understanding the genetic basis for disease
now support genetic testing
1. to confirm clinical diagnosis
2. provide additional information about familial risk.
3. genetic counseling
4. genetic information can be informative for prognosis
5. providing risk information to family members.
6. From a research perspective, genetic testing improves the
understanding of the pathophysiology of the disease and is
also a prerequisite before contemplating any gene-based
therapies.

42. 1. Retinitis pigmentosa sine pigmento
 It is characterised by all the clinical features of typical retinitis
pigmentosa, except that there are no visible pigmentary
changes in the fundus.

44. 2.Sectoral retinitis pigmentosa
It is characterised by
involvement of only one
sector of the retina.

45. 3. Pericentric retinitis pigmentosa.
 In this condition all the clinical features are similar to typical
retinitis pigmentosa except that pigmentary changes are
confined to an area, immediately around the macula.

46. 4. Retinitis punctata albescens
 It is characterised by the presence of innumerable discrete
white dots scattered over the fundus without pigmentary
changes.
 Other features are narrowing of arterioles, night blindness and
constriction of visual fields.

47. Vitamin A supplementation
 vitamin A supplementation at 15,000 IU per day suggested by
Berson et al based on a study conducted by them on 601
patients with RP.
 Currently most physicians do not advocate this treatment
considering the risk of hypervitaminosis-A, especially in
pregnant women.

48. Acetazolamide for Cystoid Macular Edema
 treatment with acetazolamide may be of benefit, with an initial
dose of 250 mg daily
 increased to 500 mg daily if no effect is apparent.

49. OPTICAL
DISTANCE
-hand held telescopes
-mounted telescopes
NEAR
Spectacles
-prismatic
-bifocals
Magnifiers
-hand held & stand
- illuminated & non-illuminated
Electronic devices

52. Gene Therapy
 Since retinitis pigmentosa arises as a consequence of
mutations in many genes, one rational approach to therapy
relies on correcting the genetic defect.
 Two approaches have been proposed:
1. delivering a normal copy of the specific affected gene to the
retina with a virus vector or other delivery method.
2. inactivating a mutated gene whose gene product has a
deleterious effect.

53. Neurotrophic Factors
 A report in 1990 showed that intraocular injection of basic
fibroblast growth factor effectively slowed photoreceptor
degeneration
 Ciliary neurotrophic factor (CNTF),delivered intravitreally has
been effective to rescue photoreceptors in multiple animal
models of retinal degeneration.

54. Stem Cell Based Therapies
 Recently, a report on the short-term use of transplanted
human-derived retinal pigment epithelial cells demonstrated
short-term safety.

55. Retinal Prostheses/Implants
 an artificial implant that would detect light, convert light
energy into an electrical signal, and then pass on that electrical
signal to other cells in the visual system that would get the
electoral signal to the brain where it could be interpreted as
vision.
 A commercial implant prototype is available in Europe and
one is currently FDA-approved for use in the United States.

56. 1. Leber’s congenital amaurosis (LCA)
2. Lawrence-Moon-Bardet-Biedl syndrome
3. Refsum’s syndrome
4. Batten’s disease
5. Cone-rod dystrophy
6. Bassen-Kornzweig syndrome (abetalipoproteinemia)
7. Cockayne’s syndrome
8. Kearns-Sayre syndrome
9. Mucopolysaccharidosis

57. PSEUDORETINITIS PIGMENTOSA
 A number of acquired conditions can cause extensive
chorioretinal atrophy that is difficult to distinguish from
advanced RP.
1. Retinal inflammatory diseases
Rubella retinopathy
Syphilis
Infectious retinitis
2. Autoimmune paraneoplastic retinopathy
3. Drug toxicity
Thioridazine
Chlorpromazine
Chloroquine
Hydroxychloroquine

58.  Retina : Stephen Ryan