Retinitis Pigmentosa

Author: Ameen Marashi, MD

History

Documentation of age along with visual loss as in retinitis pigmentosa (RP) visual loss features nyctalopia, which is presented in the first decade in autosomal recessive (AR). As for autosomal dominant (AD), the visual loss presented in the second decade combined with a constricted visual field. The visual loss in RP that may begin in the early childhood that progresses till the patient is left with tunnel vision (if the central vision remains clear).

Although the visual field defect is a characteristic for RP patients, RP patients may have a central visual loss, which can be affected in the early course of the disease, especially in AD disease [1].

Documentation of dyschromatopsia and photopsia can feature tiny shimmering next to scotomas in the mid-peripheral field but disappears when the scotomas are denser over the years.

It should be documented if the patient is a smoker along with the detailed family history is very important as questioning patients should document presence RP in first and second-degree relatives along with other systemic diseases in order to have a clue if the inheritance is AD, AR, or X-linked.

It is crucial to rule out any associations of systemic disease such as deafness, vestibular dysfunction, absorption dysfunction, spinocerebellar dysfunction, acanthocytosis, polydactyly, mental handicap, and changes in the skin such as ichthyosis.


Ocular Examination


A list of ocular examination should set

1) Best-corrected visual acuity (BCVA) for near and far is an essential step that can be performed by a trained optometrist or certified ophthalmologist to document the visual impairment, like myopia or astigmatism; however, central visual loss can be documented in patients with RP.

2) Color vision test should be obtained as defects usually noticeable by patients when vision drops below 20/40, or there is cone dysfunction in the early course of the disease.

3) Check eye movements to rule out ophthalmoplegia and ptosis, especially in patients, presented with systemic associations.

4) A slit-lamp examination done with a thorough exam of clarity and regularity of the cornea and to rule out keratoconus and any conjunctival abnormality such injection of conjunctival vessels should be documented, and any other inflammations of the conjunctiva or eyelids documented, along with iris exam and crystalline lens exam to rule out posterior subcapsular cataract which presented in the second and third decades or intraocular lens (IOL) to document the position and clarity of the posterior capsule.

5) Intra Ocular Pressure (IOP) documentation is essential as high IOP may be associated with RP patients and patients with glaucoma history. In cases of increased IOP, then gonioscopy is necessary, any associated mild to moderate glaucoma can be managed with topical antihypertensive eye drops.

Note when high IOP spotted a corrected IOP documented after central corneal thickness measurement.

6) Bilateral dilated fundus exam is essential as RP is bilateral disease and fundus exam should include a detailed examination of the optic disc, macula, posterior pole, a mid-peripheral and peripheral retinal exam with specialized indirect wide-field lenses using slit-lamp biomicroscopy or indirect ophthalmoscopy to document the following:

  • In the early course of the disease, there would be no visible intraretinal pigmentation, but with some vascular attenuation as the disease progresses, an intraretinal pigmentation in the mid periphery starting in the area surrounding the retinal vessels which become attenuated. In advanced stages of the disease, there would be a loss of pigmentation along with RPE and choriocapillaris, which make the retina look pale with the visible of larger choroidal vessels where retinal vessels become thread-like due to severe attenuation [2].

  • Macular may appear in the early course of the disease with or without early epiretinal membrane; however, in X-linked disease, a golden reflex can be noted [3], as RP progresses, a cystoid macular edema can be formed along with the progression of the epiretinal membrane which may form pre macular fibrosis along with intraretinal pigmentation in the macular area and in advanced disease macula may show atrophic changes simulating macular coloboma.

  • The optic disc may appear normal in early stages, or sometimes it appears waxy amplitude, and hyperemia with a golden ring surrounding it as the disease advances the optic disc appears pale, and the golden ring will be replaced with hyperpigmented atrophic changes, and in advanced cases, the optic disc will appear dens pale with gliosis deposits over it.

  • Some patients have intraretinal pigmentation confined to one area of the retina, which is called sector RP.

  • RP may come in the atypical form usually associated with systemic manifestation such as Usher syndrome, which presents sensorineural deafness, which can be congenital and profound as in type one with severe RP or progressive deafness with vestibular dysfunction. Type three and can have systemic features such as skeletal abnormalities and premature aging and mental handicap. Bassen-Kornzweing syndrome features absorption along with acanthocytosis and has the ocular findings of ophthalmoplegia, ptosis, squint, and nystagmus where fundus exam may show RP that may appear in clinical examination by the end of the first decade. Refsum disease features ichthyosis along with visceral and neurological disorders with salt and pepper appearance of the fundus with optic disc atrophy and may be associated with cataract. Bardet-Biedl syndrome features polydactyly with mental handicap with bull’s-eye maculopathy, and peripheral retina may look as typical RP or RP sine pigmento or retinitis punctata albescens. Kearns-Sayre syndrome, which has chronic progressive external ophthalmoplegia with ptosis and salt and pepper changes in the fundus along with systemic associations such as cardiac abnormalities, and can be associated with deafness and cerebral ataxia.

Diagnostic tests

Fundus images

It is an essential tool to document the progression of RP as in early stages; it may not show visible changes. As it progresses, it may show intraretinal pigmentation around the retinal vessels then in the mid periphery along with vascular attenuation and optic disc pallor and the macular changes that rate from the epiretinal membrane and cystoid macular edema to atrophy and pigmentation.

Optical Coherence Tomography (OCT)

OCT replaced the need of FFA to diagnose the cystoid macular edema (CME) as cystoid macular edema can appear as hyporeflective cystic spaces with increased retinal thickness with or without subretinal fluid. [6] Nevertheless, OCT is essential to document the presence of vitreomacular abnormalities such as vitreomacular traction or/and epiretinal membrane [7], OCT is essential to follow up the macular changes post-treatment.

One of the most critical features of OCT in RP patients is the loss of external retinal tissues including external limiting membrane and ellipsoid zone with thinning in the outer plexiform layer as in advanced stages of RP shows intraretinal pigmentation in the form of hyperreflective foci which is a contributing factor of reduction of vision [8]

OCT can aid the decision for visual prognosis post-cataract surgery as disruption of the ellipsoid zone has a poor visual prognosis, and the presence of CME pre surgically may get worse post-surgery.

Fluorescein Fundus Angiography (FFA)

FFA can be utilized to study cystoid macular edema [4], which appears as early capillary dilation and stellate formed leakage at the center of the fovea. However, the peripheral retinal atrophy will appear as a hyperfluorescent window defect. In contrast, intraretinal pigmentation will appear as a blocked fluorescence. In contrast, atypical RP, which has the salt and pepper changes in the retinal periphery, will appear as transmitted fluorescence and multifocal areas of choroidal atrophy [5].

Note that the physician should obtain signed consent explaining the rare complications of FFA, including death 1/200000, and FFA facility should have an emergency plan in situ.

Fundus Auto Fluorescence (FAF)

FAF shows decreased FAF in areas of RPE atrophy; in contrast, areas of persistent macular edema may show increased FAF [9].

One of the unique features of FAF is the perifoveal of increased FAF, which is a border between the functional and nonfunctional retina, which correlates disruption of IS/OS junction with thinning of outer nuclear layer outside the ring [10].

Perimetry

Kinetic perimetry can show Relative scotomas in the mid periphery; however, the visual field loss typically starts superiorly proceeded temporally then nasally and inferiorly and nasally [11] in a symmetrical fashion (for an exemption for X-linked RP) [12] in both eyes which can be severe with the progression of 4.6% of visual field loss every year as visual field loss is faster toward the retinal periphery and slower toward the center of the macula

Visual field defects began earliest between 30 to 50 degrees from fixation and which will enlarge, coalesce, and deepen and form a ring scotoma, which will constrict eventually, leaving the patient legally blind [13].

Perimetry is useful to monitor the progression of RP, especially in patients, are taking oral supplements.

Electroretinogram (ERG)

ERG is crucial for RP diagnosis, as in the early stages of RP, presented with a reduction in a- and b-wave amplitudes, but implicit time can be normal or prolonged; however, as RP progresses to advanced stages, the ERG becomes undetectable.

Other ancillary tests

Dark adaptometry is useful in detecting RP in the early stages, which shows an increased absolute rod threshold, and dark adaptation is usually prolonged [14]. However, the electrooculogram shows abnormal findings.

Managing patients with retinitis pigmentosa

Patients education

- Patients should be encouraged to cease smoking permanently; the patient advised not to get married to any his/her relatives; even patients should be encouraged to have supposed from overseas. If the patient has kids, a genetic consultation can help to determine whether the kids or other siblings are at risk of developing RP. However, genetic consultation may help to determine if the patient is at risk of systemic associations.

-The patient should be discouraged from having unnecessary dilated fundus exams as exposure to light may increase the progression of RP; this applies for sun exposure; therefore, the patient should wear protective sunglasses in cases of sun exposure.

-The physician should explain to the patient the available approved methods and procedures to improve the quality of life and to be aware of scammed non-approved treatments.

-Patients should be encouraged to have brighter light sources at home and to use night and low vision aids.

-Patients presented with atypical RP usually presented with systemic manifestations and depends on the associated systemic disease, the physician should forward the patients to a dedicated specialist for a consultation to improve the quality of patients life for example if the patient suffers from Kearns-Sayre syndrome, then patient forwarded to a cardiologist for cardiac abnormalities consultation.

Medical treatment of RP patients

-Patients can be offered to have 15000 IU/d of vitamin A with daily lutein 12 mg [15] with food rich in oily fish once a week, which is rich in DHA (docosahexaenoic acid) which may slow down visual field loss.

-The up-mentioned treatment is debatable [16], and patients should be aware that if accepted to take oral supplements, then the patient should monitor liver function and vitamin A levels. If the patient is a smoker, then the patient should stop smoking.

-This oral supplements regime should be avoided in pregnant patients due to increased teratogenic risk.


In the case of cystoid macular edema

-Cystoid macular edema is one of the main causes of central visual loss in patients with RP and can be treated topical Dorzolamide t.i.d. If this fails, then oral Acetazolamide 250 mg b.i.d. and in case a recurrence of cystoid macular edema, then treatment is repeated, and the patient advised to have oral Acetazolamide 125 mg b.i.d [17].

-Oral Acetazolamide may cause hand tingling and fatigue, but it is more effective than topical Dorzolamide and may have better visual outcomes [18].

-In cases that cystoid macular edema persists to oral and topical treatment, then intravitreal steroids such as triamcinolone or dexamethasone implant can be used. Still, intravitreal steroids may need repeated treatment with an increase of intraocular pressure and cataract formation [19].

In cases presented with significant cataract

When scheduling cataract surgery for RP patients, special consideration should be taken into account. OCT should be obtained to assess the ellipsoid zone and outer retinal tissue integrity and to rule out any other macular pathologies, as loss of ellipsoid zone and other atrophic changes yells bad visual prognosis. Nevertheless, the presence of cystoid macular edema pre-surgery may get worse after cataract surgery. Another test can be done to put the patient on two weeks dilated iris and assess if the patient had better visual acuity, as this may predict if the patient can benefit from cataract surgery [20].

The patient should understand that cataract surgery won’t improve visual fields nor influence the progression of the disease [21].

The patient should have a realist expectation for visual outcome post-surgery [22].


Surgical options for RP patients

-The patient presented with vitreomacular abnormalities such as an epiretinal membrane or/and vitreomacular traction may benefit from pars plana vitrectomy with ILM peeling, especially if the ellipsoid zone and outer retinal tissue are intact [23].

-Patients who have tested positive for RPE 65 genetic test (Leber variant) are confirmed to have better visual outcomes when Luxturna injected submacular; however, this therapy may not restore normal vision and may not persist forever [24].


Flow chart summarizes the approach for retinitis pigmentosa

Follow up and prognosis


- Patients may have visual impairment below 20/200 within 4 to 10 years. X-linked RP patients may get blind by year 30 to 40. Though patients with AD RP may end up with beneficial vision beyond sixty in contrast to AR and X-linked RP patients. However, sector RP has a better visual prognosis than other types of RP patients [25].

-Presence of macular geographic atrophy or bull's eye is associated with loss of 3 to 4 lines of vision within five years; however, RP patients treated for cystoid macular edema can improve vision and treatment efficacy should be evaluated using OCT [26].

- In cases of cataract surgery, the patient should be put on topical steroids and nonsteroidal anti-inflammatory drugs for a longer extent than normal individuals. The surgeon should try not to manipulate the iris as those patients are prone to inflammation and should be followed up with OCT to rule out post pseudophakic cystoid macular edema. However, the improvement of vision after cataract surgery is two lines by 83% [21].

References

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24. Darrow JJ Luxturna: FDA documents reveal the value of a costly gene therapy. Drug Discov Today. 2019 Apr;24(4):949-954. doi: 10.1016/j.drudis.2019.01.019. Epub 2019 Jan 31

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These guidelines were reviewed and updated in September 2020