Which cell population shows the predominant early dysfunction in retinitis pigmentosa?

Rod photoreceptors Retinitis pigmentosa is a heterogeneous group of inherited retinal disorders with diffuse progressive dysfunction predominantly of rod photoreceptors; cones and the retinal pigment epithelium degenerate subsequently.

Retinitis pigmentosa characteristically presents with which pattern of visual loss?

Night blindness with progressive visual field loss Visual impairment in retinitis pigmentosa usually manifests as night blindness and progressive visual field loss, in keeping with the early rod-predominant dysfunction.

Sudden painless loss of central vision

Fluctuating blur that is worse in bright light

Painful colour vision loss with central scotoma

Approximately what proportion of patients with retinitis pigmentosa develop cystic macular lesions?

30% About 30% of retinitis pigmentosa patients develop cystic macular lesions, and these are the subgroup in whom carbonic anhydrase inhibitors or intravitreal steroids may help.

Which agents have shown benefit for cystic macular lesions in retinitis pigmentosa?

Oral prednisolone with topical atropine

Topical timolol with oral pilocarpine

Oral doxycycline with topical cyclosporine

In the Berson randomized trials of supplements in retinitis pigmentosa, which showed the fastest decline in ERG amplitude?

High-dose vitamin E Higher doses of vitamin A palmitate were associated with the slowest decline in ERG amplitude, whereas high-dose vitamin E showed the fastest decline.

Lutein added to high-dose vitamin A and DHA in retinitis pigmentosa significantly slowed decline on which measure?

HFA 60-4 total point score Lutein 12 mg/day with high-dose vitamin A and DHA left the rate of decline of the HFA 30-2 total point score unaffected, but had a significant effect on the rate of decline of the HFA 60-4 total point score.

30-Hz cone flicker ERG amplitude

Dietary management of retinitis pigmentosa due to Refsum disease centres on restricting which component?

Phytanic acid-containing foods Refsum disease requires restriction of phytanic acid-containing foods, whereas hereditary abetalipoproteinemia is managed with a low-fat diet.

FDA-approved gene therapy in retinitis pigmentosa targets mutations in which gene?

RPE65 Gene therapy for RPE65 mutations has received FDA approval and offers the prospect of improved functional vision, particularly in younger patients.

The Orion implant being investigated for end-stage retinitis pigmentosa places its electrodes in which site?

Visual cortex of the brain Unlike the epiretinal ARGUS II, whose manufacture has been discontinued, the Orion implant places electrodes into the visual cortex of the brain and remains under investigation.

Epiretinal surface of the macula

Subretinal space under the fovea

Suprachoroidal space at the equator

RETINITIS PIGMENTOSA: management and complications

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders characterized by diffuse progressive dysfunction of predominantly rod photoreceptors with subsequent degeneration of cone photoreceptors and the retinal pigment epithelium.

Visual impairment usually manifests as night blindness and progressive visual field loss. Retinitis pigmentosa (RP) may be seen in isolation (typical RP) or in association with systemic disease.

General treatment

Many treatments have been explored without proven benefit for the isolated forms of Retinitis pigmentosa (RP).

These include various vitamins and minerals, vasodilators, tissue therapy with placental extract, cortisone, cervical sympathectomy, injections of a hydrolysate of yeast RNA, ultrasound, transfer factor, dimethyl sulfoxide, ozone, muscle transplants, and subretinal injections of fetal retinal cells.

None of the above treatments were conducted in randomized, controlled clinical trials. It is important to note that anecdotal treatment with a subjective improvement of the visual function should be interpreted with caution due to fluctuation in visual acuity and visual fields in this disease.

ERG is a better objective measure of remaining retinal function. Any potential therapy will likely require several years of follow-up to assess efficacy due to the nature of the slow progression of this disease.

Medical therapy

Controversies surround the use of high-dose vitamin A, docosahexaenoic acid (DHA), and lutein to slow the progression of Retinitis Pigmentosa (RP).

Berson et al. conducted three large randomized trials involving 601 adult patients, assessing outcomes such as the 30-Hz cone flicker ERG.

Retinitis pigmentosa

Results indicated that higher doses of vitamin A palmitate exhibited the slowest decline in ERG amplitude, contrasting with high-dose vitamin E, which showed the fastest decline.

DHA supplementation, while not impacting RP over a 4-year interval, did show potential benefits for those starting vitamin A for the first time, slowing visual field and ERG amplitude loss in initial years.

In another study, lutein (12 mg/day) combined with high-dose vitamin A and DHA showed mixed results. While the rate of decline in the total point score for the HFA 30-2 program remained unaffected, a significant effect was observed on the rate of decline for the HFA 60-4 total point score.

Despite these findings, debates persist regarding the interpretation of study outcomes, emphasizing the need for cautious consideration of high-dose vitamin A and supplements due to potential side effects.

Test your knowledge 10 questions from this article

Treatment Considerations and Follow-up

For patients developing cystic macular lesions (about 30%), potential benefits have been identified with oral acetazolamide, topical dorzolamide or brinzolamide drops, and intravitreal steroids in some cases.

Intravitreal anti-VEGF injections have also demonstrated effectiveness in select cases. Light deprivation has not proven beneficial, but the use of ultraviolet and short-wavelength blocking sunglasses for outdoor activities is generally advised.

Annual ocular examinations are typically sufficient for measuring visual acuity and Goldmann’s visual field. However, initiation of medical treatment may necessitate more frequent visits and laboratory blood work.

Annual assessments of vitamin A levels and liver function are recommended for patients undergoing treatment, considering potential complications.

Treatment of Rare Forms and Future Directions

Patients with hereditary abetalipoproteinemia and Refsum disease necessitate unique treatment approaches, emphasizing low-fat diets and restricting phytanic acid-containing foods, respectively.

Future directions in RP management include gene therapy, with adeno-associated virus (AAV) based gene transfer showing promise in animal models and humans with specific genetic mutations.

Ciliary neurotrophic factor (CNTF) has demonstrated the ability to slow retinal degeneration in animal models, but its long-term efficacy in humans remains inconclusive.

Retinal prostheses, such as the FDA-approved ARGUS II implant, show potential for patients with end-stage RP, while gene therapy for RPE65 mutations has received FDA approval, offering hope for improved functional vision in younger patients.

Surgical Interventions

Surgical options include the ARGUS II implant for end-stage RP patients, stimulating the retina electrically and providing subjective improvements in mobility.

The Orion implant, focusing on electrodes placed into the visual cortex of the brain, is currently under investigation. Notably, while the ARGUS II implant has shown positive outcomes, the manufacturing has been discontinued, redirecting efforts toward the Orion implant.

If cataracts develop, surgical removal is generally deferred until the patient’s ability to read with a better eye diminishes. Cataract surgery has demonstrated significant improvements in visual acuity for RP patients.

Complications and Safety Measures

Toxicity from vitamin A treatment is rare but requires monitoring, with pretreatment assessments and annual checks of fasting serum vitamin A levels and liver function.

High doses of vitamin A should be avoided during pregnancy due to potential birth defects. Long-term supplementation in older adults may impact bone density, necessitating consultation for postmenopausal women and men over 49.

Patients with renal issues or on chronic doxycycline should avoid vitamin A supplementation due to potential complications.

The 5-year study of the ARGUS II implant supports its long-term safety and benefits, with complications such as conjunctival erosion and hypotony being rare but not impossible, emphasizing the need for vigilant monitoring.

As surgical and medical approaches evolve, optimizing patient outcomes remains a collaborative effort requiring ongoing research and careful consideration of individual patient needs.

References

da Cruz L, Coley BF, Dorn J, Merlini F, Filley E, Christopher P, Chen FK, Wuyyuru V, Sahel J, Stanga P, Humayun M, Greenberg RJ, Dagnelie G; Argus II Study Group. The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss. Br J Ophthalmol 2013 May;97(5):632-6.
Luo YH, Zhong JJ, da Cruz L. The use of Argus® II retinal prosthesis by blind subjects to achieve localisation and prehension of objects in 3-dimensional space. Graefes Arch Clin Exp Ophthalmol. 2014 Dec 31. [Epub ahead of print].
Stronks HC, Dagnelie G. The functional performance of the Argus II retinal prosthesis. Expert Rev Med Devices. 2014 Jan;11(1):23-30..
Bastek JV, Heckenlively JR, Straatsma BR. Cataract surgery in retinitis pigmentosa patients. Ophthalmology 1982;89(8):880-884.
Feskanich D, Singh V, Willett WC, Colditz GA: Vitamin A intake and hip fractures among postmenopausal women. JAMA. 2002;287(1):47-54.
Michaelsson K, Lithell H, Vessby B, Melhus H: Serum retinol levels and the risk of fracture. N Engl J Med. 2003;348(4):287-294.
deCruz et al. Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis. Ophthalmology. 2016 Oct;123(10):2248-54.

Test yourself

A few questions straight from this article.

1 / 10 0 correct

Which cell population shows the predominant early dysfunction in retinitis pigmentosa?
Retinitis pigmentosa is a heterogeneous group of inherited retinal disorders with diffuse progressive dysfunction predominantly of rod photoreceptors; cones and the retinal pigment epithelium degenerate subsequently.
Retinitis pigmentosa characteristically presents with which pattern of visual loss?
Visual impairment in retinitis pigmentosa usually manifests as night blindness and progressive visual field loss, in keeping with the early rod-predominant dysfunction.
Which test provides the better objective measure of remaining retinal function in retinitis pigmentosa?
Visual acuity and visual fields fluctuate in retinitis pigmentosa, so subjective improvement must be read cautiously; ERG is the better objective measure of remaining retinal function.
Approximately what proportion of patients with retinitis pigmentosa develop cystic macular lesions?
About 30% of retinitis pigmentosa patients develop cystic macular lesions, and these are the subgroup in whom carbonic anhydrase inhibitors or intravitreal steroids may help.
Which agents have shown benefit for cystic macular lesions in retinitis pigmentosa?
Potential benefit has been identified with oral acetazolamide, topical dorzolamide or brinzolamide drops, and intravitreal steroids; intravitreal anti-VEGF has also been effective in select cases.
In the Berson randomized trials of supplements in retinitis pigmentosa, which showed the fastest decline in ERG amplitude?
Higher doses of vitamin A palmitate were associated with the slowest decline in ERG amplitude, whereas high-dose vitamin E showed the fastest decline.
Lutein added to high-dose vitamin A and DHA in retinitis pigmentosa significantly slowed decline on which measure?
Lutein 12 mg/day with high-dose vitamin A and DHA left the rate of decline of the HFA 30-2 total point score unaffected, but had a significant effect on the rate of decline of the HFA 60-4 total point score.
Dietary management of retinitis pigmentosa due to Refsum disease centres on restricting which component?
Refsum disease requires restriction of phytanic acid-containing foods, whereas hereditary abetalipoproteinemia is managed with a low-fat diet.
FDA-approved gene therapy in retinitis pigmentosa targets mutations in which gene?
Gene therapy for RPE65 mutations has received FDA approval and offers the prospect of improved functional vision, particularly in younger patients.
The Orion implant being investigated for end-stage retinitis pigmentosa places its electrodes in which site?
Unlike the epiretinal ARGUS II, whose manufacture has been discontinued, the Orion implant places electrodes into the visual cortex of the brain and remains under investigation.