Management
Currently, there is no known effective treatment that can prevent or reverse the vision loss in RP. Standard treatment modalities remain to be established
1. General recommendations
Supportive measures to maintain and/or improve quality of life should be provided to all individuals affected by RP. Low vision rehabilitation and optical aids should be proposed, including high-intensity lamps, contrast enhancing filters, infrared blocking sun lenses, magnifiers (such as closed circuit televisions). Compensation of the restricted visual field could be achieved by scanning training, minus lenses, reverse telescopes and prisms. In case of profoundly constricted fields, mobility training should be advised.
Patients with RP are advised to wear low wave length blocking sunglasses (as dark as can be tolerated without compromising vision) with tinted side shields outdoors during the day. For example: CPF 550 lenses (Corning Photochromatic Filter manufactured by Corning Glass Works), which filter out 97-99% of the spectral and ultraviolet energy below 550 nm wavelength. Reduction in light exposure, especially stressful light exposure, is beneficial. Prolonged light deprivation, however, has little or no effect on the disease course.
Regular eye exams are necessary to track the rate and degree of deterioration. Assessment of visual fields, cataract or macular edema should be performed on annual basis. ERG evaluation is periodic, every 2-3 years.
Psychological counseling is appropriate as it provides education and support to patients and their families. Patients should understand the variable, slowly progressive course of the disease that leads to bilateral, initially peripheral and later central vision loss. Patients should be carefully advised about their ability to drive a motor vehicle, especially under dimly lit conditions, such as night driving.
2. Treatment modalities
Medication
Photoreceptor function can be potentially preserved by administration of vitamin A palmitate, lutein, docosohexanoic acid (DHA), calcium-channel blockers. The precise mechanism(s) of the possible supportive role of these medications in retinal degenerations remains unclear.
The most widely recognized nutritional supplement for RP patients is vitamin A palmitate, which has been shown to slow the rate of retinal degeneration. Currently, adult patients (over the age of 18) with common forms of RP and good general health are recommended to take vitamin A palmitate under medical supervision. The suggested dosage regimens vary (15,000 IU/day or 50,000 UI once a week or 50,000 UI every 2 weeks). Patients should avoid the concomitant use of high doses of vitamin E, as paradoxally it can increase the deterioration rate, probably due to reduced availability of other vitamins in the retina. Patients should be aware of the benefits/risks expectations associated with vitamin A treatment. On one hand, though vitamin A therapy may slow the progression of the disease, it has not been shown to improve the visual acuity or visual field. On the other hand, high doses of vitamin A may be teratogenic and can potentially cause liver damage. It also increases the risk of lung cancer in case of tobacco consumption. As a consequence, female patients should be advised to cease therapy if they are planning to or become pregnant. Regular check of liver enzymes should also be recommended. Beta-carotene alone can be used to replace vitamin A therapy. Patients should also be advised of the importance of a well-balanced diet including leafy green vegetables and omega-3 fatty acids for further benefits.
Recently, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid commonly found in fish, has been investigated in RP treatment. Further reduction in the rate of retinal degeneration has been shown upon DHA treatment (1200 mg/d) in patients recently placed on vitamin A palmitate therapy. However, the beneficial effects of DHA do not usually extend beyond a treatment period of two years.
Lutein and/or zeaxanthin (macular pigments from dietary sources), 20 mg/d for six months, have been shown to increase macular pigment in approximately 50% of individuals with RP, without change in central vision. The long-term effects of this supplementation have yet to be evaluated.
Some studies have demonstrated that calcium channel blockers (e.g. diltiazem) inhibit the photoreceptor degeneration. Neuroprotective effects of these drugs have been shown in several forms of RP only and seem to be restricted to certain mutations and/or model studied and/or the calcium channel blocker used.
Some anti-Parkinson's drugs with antiapoptotic properties have been included in the treatment of RP. The value of this option remains to be evaluated.
Cystoid macular edema that may cause significant additional loss of visual function in patients with RP have been shown to respond to oral or topical (less effective) carbonic anhydrase inhibitors, e.g. acetazolamid. If the macular edema is severe and unresponsive to acetazolamide, local injections of corticosteroids could be considered although their efficacy is still under discussion.
Cataract surgery
As a general guideline, cataract surgery should be performed as soon as it causes significant impairment of vision. It should not be deferred too long, thus the patient would benefit from the surgery before the evolution of the retinal disease limits the postoperative recovery. The surgical procedure itself is not more complicated than regular cataract removal from an eye with no retinal degeneration. One might be cautious in case of preexisting macular edema and the surgery should be postponed until resolution of the edema. There is no real evidence that retinal degeneration is hastened or macular edema triggered by the surgery but postoperative follow-up should detect such complications. Patients should be educated about reasonable expectations of cataract extraction, as cataract surgery in young adults and cataract surgery in both eyes in patients with advanced RP may be sometimes compromised.
The inheritance modes of RP include autosomal dominant (ad), autosomal recessive (ar), X-linked (xl), digenic and mitochondrial patterns. Because of the variation in both the nature of the penetrance and expressivity of the genes coding for RP, ocular manifestations widely vary among the inherited modes and even among members within the same family.
Autosomal recessive RP (arRP) is the most frequently inherited type of RP, accounting for approximately 20-30 % of cases with approximately 25 arRP genes identified so far. Mutations in RPE65, PDE6A and PDE6B cause 2-5 % of arRP cases, while mutations in USH2A, which can also cause Usher syndrome, may account for up to 5% of arRP cases. Autosomal recessive RP occurs when both parents are unaffected carriers of the same defective gene. The chance of a child being affected is one in four.
Autosomal dominant RP (adRP) is the second most frequently inherited type of RP, accounting for approximately 15-20 % of cases. Twenty adRP genes have been identified to date (see http://www.sph.uth.tmc.edu/Retnet/). Three genes, RHO, RP1 and PRPH2, account for approximately 25-30 %, 5-10 % and 5-10 % of adRP cases, respectively. More than 100 RHO mutations have been reported so far, causing variation within the clinical presentations. In adRP, typically, one of the parents is affected by the disease. The chance is one in two of any given offspring being affected by the disease, if the affected parent has one normal and one defective gene.
X-linked RP (xlRP) is the least frequently inherited type of RP, accounting for 6-10 % of cases. Two genes and two additional loci have been identified to date. Mutations in RPGR (also called RP3) and RP2 are the most common causes of xlRP, accounting for 70-90% and 10-20%, respectively, of the xlRP cases. X-linked recessive RP may occur in offspring in two ways. The father can be affected or mother can be carrier of the defective gene. If the father is affected, all sons will be unaffected and all daughters will be carriers. If the mother is the carrier, one in two sons will be affected and one in two daughters will be carriers. In families with xlRP, males are affected; females carry the genetic trait and usually do not experience serious vision loss. However, they can manifest a milder form of the disease.
Very rare modes of inheritance include digenic and mitochondrial DNA patterns. Digenic RP is caused by the simultaneous presence of a mutation in the PRPH2/RDS gene and a mutation in the ROM1 gene.
Regarding family planning issues, the optimal time for determination of genetic risk is before pregnancy. Prenatal testing and preimplantation genetic diagnosis may be available for families in which the disease-causing mutation(s) has been identified in an affected family member.
