Managing a Case of Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a group of inherited progressive retinal degenerations affecting photoreceptors and the retinal pigment epithelium (RPE).^1-3 Although more than 250 genes and 4,500 mutations are known to be associated with RP, it is estimated that 50% or more genes may still be unaccounted for.¹ Inheritance patterns for RP include early onset (5%), X-linked (10-15%), autosomal recessive (15-20%), autosomal dominant (20-25%), and sporadic (30%).^1,3 The inability to broadly predict prognosis in patients with RP can be challenging for both patients and clinicians, and diagnosis is complicated by a high degree of genetic, allelic, phenotypic, and clinical heterogeneity (Table).^1,2

The following case and discussion illustrate the importance of genetic testing and referral to low vision resources when you suspect a patient may have RP.

CASE REPORT

A 38-year-old male presented to our clinic with complaints of blurry vision and difficulty navigating environments, leading him to bump into and trip over objects. He also noted difficulty reading despite wearing glasses.

His ocular history was significant for RP, which he had been diagnosed with at 17 years of age. His medical history was significant for bipolar disorder. His medications included trazodone, benztropine, risperidone, ibuprofen (prn), and acetaminophen (prn). His family ocular history included a brother with known inherited retinal degeneration, and he denied alcohol and drug use but reported smoking half a pack of cigarettes daily.

CLINICAL FINDINGS

The patient’s entering VA was 20/40 OU with his habitual spectacle prescription. His pupils were equal, round, and reactive to light, without afferent pupil defect, and the extraocular motilities were full range of motion OU. The confrontation visual fields were tightly constricted 360° OU. Goldmann visual field testing was able to quantify a visual field constriction of approximately 5˚ OU (Figure 1). Refraction yielded a low myopic prescription that led to minimal improvement in visual acuity OU. The patient’s external ocular examination was unremarkable OU. His IOP was 15 mm Hg OD and 18 mm Hg OS with rebound tonometry. A dilated retinal examination revealed extensive peripheral bone spicules and macular pigmentation OU consistent with an RP diagnosis (Figure 2). Fundus autofluorescence highlighted the retinal pigmentary changes consistent with RP (Figure 3), and OCT scans confirmed atrophy of the macula OU without evidence of cystoid macular edema (CME) OU (Figure 4).

NEXT STEPS

The patient was evaluated in our low vision department and was provided with multiple assistive devices, including an LED headlamp, a handheld magnifier, plum-colored Solar Shield filters (Eschenbach Optik of America), and a MaxTV Clip (Eschenbach Optik of America). He was also referred for orientation and mobility instruction and activities of daily living instruction and was educated on smartphone applications for magnifying print.

Genetic testing was ordered, which demonstrated that he was positive for a PROM1 gene mutation, known to be associated with RP. Genetic counseling was provided by the genetic testing company.

RP BACKGROUND

Common symptoms associated with RP include nyctalopia, constriction of visual fields, blurry vision, reduced color vision discrimination, and occasional photopsias, while classic signs include retinal bone spicules, waxy pallor of the optic discs, attenuated retinal vessels, CME, and posterior subcapsular cataracts.^1,2

RP can be classified into rod-cone dystrophies (80-90%), where rods are primarily affected before cones, or cone-rod dystrophies (10-20%), where cones are primarily affected before rods.^1,2 Approximately 85% of RP cases are nonsyndromic, or isolated, and about 15% of cases involve syndromes affecting multiple systemic areas (also known as syndromic RP), the most common being Usher syndrome, which leads to RP and hearing loss.^1,3 Other possible associated systemic conditions include Bardet-Biedl syndrome, Refsum disease, Laurence-Moon syndrome, Alström syndrome, Cockayne syndrome, Friedreich ataxia, and mucopolysaccharidosis.^1,2

Photoreceptor cell death is the ultimate cause of vision loss in RP.³ The PROM1 gene encodes for a transmembrane glycoprotein in retinal photoreceptor cells,⁵ and PROM1 mutations in RP result in amino acid substitutions leading to abnormal proteins in retinal photoreceptors, thus causing retinal degeneration and dysfunction.⁵

Visual acuity in RP can vary widely, ranging from 20/20 to total blindness.^1,2 Most commonly, visual fields are constricted, leaving a small central island of vision, but central scotomas can also occur.^1,2 Visual field loss typically progresses by approximately 4% to 12% annually.⁴ Visual prognosis is difficult to predict in many patients¹; age of onset, progression rates, and severity of disease in RP are extremely variable and appear to be dependent on both known and unknown factors.^1,2 Most patients develop this condition in the first or second decades of life,⁴ while visual impairment may occur around 40 to 50 years of age.^1,3

Notes on Diagnosis and Management

Routine examination and imaging for RP may include visual acuity testing, color vision testing, standard visual field testing, microperimetry, fundus photography, fundus autofluorescence, OCT, electrophysiology (ie, full-field and multifocal electroretinogram), and genetic testing.^1,3,6 We did not pursue electrophysiology testing for this patient, as we did not feel it would have added much information to what we already learned from the clinical examination, fundus photography, OCT, and genetic testing.

A referral to low vision rehabilitation (LVR) is essential to address the functional needs and quality of life in patients with RP. Although a referral to low vision may be intuitive for patients presenting with severe visual impairment, it is highly encouraged that a low vision referral be made early in the disease process, even before significant visual impairment occurs,⁷ as impaired visual function may occur before a measurable decrease in high contrast visual acuity is noted. Additionally, addressing even a mild reduction in visual acuity has been shown to increase quality of life.⁸

As patients with RP develop more advanced disease, leading to significant visual field loss, central vision loss due to the development of polar cataracts or cystoid macular degeneration and glare sensitivity both inside and outside are additional complications that may impair visual function. To assess functional visual impairment, it is important to ask direct questions about entoptic phenomena, such as photopsia.⁹ According to a study of 500 patients by Heckenlively et al, the second most common problem affecting 34.6% of patients with RP was light flashes.¹⁰ These patients also need to be evaluated carefully to rule out other conditions that may cause similar symptoms, such as retinal detachments.

Beware of CBS

It is important to consider the possibility of hallucinations with vision loss, or Charles Bonnet syndrome (CBS), and to include direct questions about CBS in the patient’s low vision examination history. Hallucinations associated with CBS may occur in those who have reduced visual acuity, contrast sensitivity impairment, visual field loss, or monocular vision loss.¹¹ The reported prevalence of CBS varies widely among patients with ophthalmologic disorders from 15% to 60%.¹¹

According to a study by Crumbliss et al, 12 of 50 patients (24%) had visual hallucinations typical of CBS; six of these 12 patients (50%) had daily recurring hallucinations.¹² They also found that once the patients were made aware of CBS and reassured that it was normal to experience this phenomenon with vision loss, their anxiety decreased. It is also thought that LVR may help decrease the frequency of CBS hallucinations.

BENEFITS OF LVR

LVR has been shown to be beneficial for the psychosocial well-being of patients with vision loss; peer support groups have been shown to be important as well. Such psychological therapies, including support groups, should be recommended for patients with vision loss, in consultation with the individual patient.^13,14 Good psychosocial well-being, even early in vision loss, may significantly improve anxieties associated with disability.¹¹

Although referral to a low vision provider is always appropriate for patients with RP, the primary care optometrist may consider treatment options that can also be accomplished within a general practice as a bridge to LVR services. For patients with RP without significant visual acuity or visual field loss, simply providing the proper lens tint or filter can aid in the patient’s visual comfort and quality of life. Tints and filters that absorb short wavelength light (ie, shorter than 450 nm) have been shown to provide the most benefit.¹⁵ An in-office filter assessment can identify the correct filter for contrast enhancement and glare reduction.¹⁶ Retinal bleaching and slowed visual recovery when transitioning between differently illuminated environments are common symptoms in patients with RP; providing a filter reduces the demand on the RPE by filtering out higher-wavelength light.¹⁷

OTHER TREATMENT OPTIONS

Treatment options for RP in the literature beyond low vision consultation and genetic testing/counseling include pharmacologic interventions, such as vitamin A supplementation, carbonic anhydrase inhibitors, steroids, anti-VEGF therapy, valproic acid, ciliary neurotrophic factor, voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics), and retinal implants.^3,4 Voretigene is FDA-approved for RPE65 mutations and, thus, was not a viable treatment option in this particular case.¹⁸ Promising future treatment options may include stem cell-based and gene therapies.^3,4

ADDRESS VISUAL PROBLEMS EARLY

This case highlights the importance of low vision consultation and genetic testing options for patients with RP. The diagnosis of RP was not necessarily the most difficult part of this patient’s care. Rather, addressing his functional vision needs with the use of low vision devices was the major action that benefitted the patient in this case.

As genetic testing becomes more popular with inherited retinal diseases, eye care providers should have a lower threshold for referring for low vision services, as well as ordering genetic testing services for patients with RP.