What is the etiology, location, and management of retinitis pigmentosa (RP) in an elderly patient?

Retinitis Pigmentosa: Etiology, Location, and Management in Elderly Patients

Etiology

Retinitis pigmentosa is a heterogeneous group of inherited retinal degenerations caused by mutations in over 45 genes, with the RHO, RP1, and RPGR genes contributing the greatest number of known causative mutations. 1, 2, 3

• Inheritance patterns include autosomal dominant, autosomal recessive, X-linked, digenic forms, and sporadic cases, with approximately 60% of RP cases still having no identified genetic cause 2, 3

• Pathophysiology involves primary photoreceptor cell degeneration, predominantly affecting rod cells in the peripheral retina first, followed by progressive cone cell loss 1, 2, 4

• The disease displays extensive clinical and genetic heterogeneity, with no single mutation accounting for more than 10% of unrelated patients 3

Location and Clinical Manifestations

RP primarily affects the peripheral retina initially, with characteristic retinal pigment epithelial changes visible on fundus examination, including bone spicule pigmentation, retinal vessel attenuation, and waxy optic nerve pallor. 2, 4

Anatomical Distribution

• Rod-cone dystrophy (most common form) begins in the peripheral retina with night blindness as the first symptom, followed by progressive peripheral visual field loss in daylight 2

• Cone-rod dystrophy (less common presentation) affects central vision first, with decreased visual acuity predominating over visual field loss 2

• Fundus findings include retinal pigment epithelial hypo- or hyperpigmentation ("salt-and-pepper" appearance), retinal granularity, bone spicule formation, narrowed retinal vessels, and waxy optic nerve head pallor 4

Complications Affecting the Macula

• Cystoid macular edema (CME) occurs in 10-20% of patients on fluorescein angiography and up to 49% on optical coherence tomography, causing additional central visual acuity loss 1

• CME can manifest at any stage of disease, may be unilateral or bilateral, and is more frequently associated with CRB1 gene mutations 1

Management Algorithm

Diagnostic Confirmation

• Clinical diagnosis requires documentation of night blindness, peripheral visual field defects, characteristic fundus lesions, and hypovolted electroretinogram traces with progressive worsening 2

• Electroretinography is essential to demonstrate rod and cone photoreceptor dysfunction and monitor disease progression 4

• Optical coherence tomography should be performed to detect macular edema, which represents one of the few treatable complications 1

Treatment Approach

Currently, there is no therapy that stops disease progression or restores vision in RP, making the visual prognosis poor, with treatment restricted to slowing degeneration, managing complications, and addressing psychosocial impact. 2, 5

For Cystoid Macular Edema (The Primary Treatable Complication)

• First-line therapy: Systemic carbonic anhydrase inhibitors—oral acetazolamide or topical dorzolamide—remain the mainstays of initial treatment 1

• Second-line therapy: If CME is refractory to acetazolamide, intravitreal corticosteroid injections may be considered 1

• Avoid anti-VEGF injections: These have limited effect in RP-associated CME and should be avoided 1

• Vitrectomy: Role remains undetermined, with variable benefits among patients 1

General Disease Management

• Sunlight protection and vitamin A supplementation may slow the degenerative process, though evidence is limited 2

• Cataract surgery when indicated, as cataracts are a common complication 2

• Vision rehabilitation services are critical, as RP severely impacts daily tasks, employment, and independence, with greater emotional and psychological impact than diabetic retinopathy or age-related macular degeneration 5

Gene Therapy (Limited Availability)

• Voretigene neparvovec (Luxturna®) is the only curative intervention, but it is applicable to only 1-6% of patients with specific RPE65 gene mutations 5

Critical Clinical Considerations

• Genetic counseling is always advised given the inherited nature of the disease 2

• Molecular diagnosis is not routinely performed due to tremendous genetic heterogeneity, though it may be considered for family planning purposes 2, 3

• Prevalence is approximately 1 in 3,500 to 1 in 4,000 people worldwide, making it the leading cause of visual disability and blindness in subjects less than 60 years old 2, 5

• Most patients will experience reduced quality of life with high carer burden arising from psychological and financial stress 5

• Prognosis: Permanent visual loss or blindness is the ultimate consequence, usually occurring after midlife, though some cases may have rapid evolution over two decades or slow progression that never leads to complete blindness 2, 3