Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review

There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa; however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (including acetazolamide and methazolamide) and topical carbonic anhydrase inhibitors (dorzolamide and brinzolamide) are effective first-line treatments. In patients unresponsive to carbonic anhydrase inhibitor treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implants), oral corticosteroid (deflazacort), intravitreal antivascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to retinitis pigmentosa. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first-line treatment in CME secondary to retinitis pigmentosa. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME.     

Bilateral Intravitreal Dexamethasone Implant for Retinitis Pigmentosa-Related Macular Edema

Purpose

To report the efficacy of intravitreal dexamethasone implant in a patient with retinitis pigmentosa and bilateral cystoid macular edema unresponsive to topical carbonic anhydrase inhibitors.

Case Report

A 36-year-old man with bilateral cystoid macular edema associated with retinitis pigmentosa that was unresponsive to topical carbonic anhydrase inhibitors underwent bilateral 0.7-mg intravitreal dexamethasone implants two weeks apart. Spectral domain optical coherence tomography revealed resolution of macular edema one week following each injection in both eyes and his visual acuity improved. However, macular edema recurred two months later in OS and three months later in OD. Second implant was considered for both eyes. No implant-related complication was experienced during the follow-up of seven months.

Conclusion

Inflammatory process seems to play a role in retinitis pigmentosa. Intravitreal dexamethasone implant may offer retina specialists a therapeutic option especially in cases unresponsive to other treatment regimens in eyes with retinitis pigmentosa-related macular edema.Key words: Intravitreal dexamethasone implant, Retinitis pigmentosa, Macular edema     

The role of carbonic anhydrase inhibitors in the management of macular edema

Medical treatment of cystoid macular edema (CME) with carbonic anhydrase inhibitors has been known for over a decade. Initial observations were based on experimental data which suggested that acetazolamide can increase fluid absorption across the retinal pigment epithelium. Carbonic anhydrase inhibitors (CAI) have also been shown to have other direct effects both on retinal and retinal pigment epithelial cell function by inducing an acidification of the subretinal space, a decrease of the standing potential as well as an increase in retinal adhesiveness. It is thought that acidification of the subretinal space is finally responsible for the increase in fluid resorption from the retina through the RPE into the choroid. Several clinical studies have suggested that patients with cystoid macular edema due to retinitis pigmentosa and uveitis may react more favorably to CAI treatment than other etiologies such as diabetic maculopathy or macular edema after retinal vein occlusion. The present working hypothesis is that diffuse leakage from the RPE responds more readily to CAI treatment than leakage from retinal vessels. This may be due to the modulation of membrane- bound CA IV in the RPE which may have lost its polarised distribution in the presence of macular edema. A normal clinical starting dose of CAI is 500 mg/day which should be continued for at least one month to see an effect. This dose may be reduced by the patients over the course of therapy. Metaphylaxis to the drug may occur with a rebound of the edema despite continuation of treatment. This revised version was published online in July 2006 with corrections to the Cover Date.     

Efficacy of topical brinzolamide in children with retinal dystrophies

ABSTRACT

Background: Inherited retinal dystrophies are a leading cause of irreversible blindness in children in the United States. Topical carbonic anhydrase inhibitors have improved central vision and cystoid macular edema in patients with retinal dystrophies, but few studies have assessed their efficacy in children.

Materials and Methods: A retrospective chart review was performed with Institutional Review Board approval to identify pediatric patients with inherited retinal dystrophies who received topical brinzolamide at a single university center between 2008 and 2015. Serial visual acuity and central macular thicknesses were compared to assess the efficacy of brinzolamide.

Results: Seven subjects were identified who met the inclusion criteria. Four had juvenile X-linked retinoschisis, two had retinitis pigmentosa, and one had Leber congenital amaurosis. All were prescribed brinzolamide thrice daily; however, one patient was completely non-compliant. Four of the six treated patients exhibited a mild decrease in central macular thickness in both eyes during the study with all six treated patients having significantly improved vision at the first endpoint, 33.2 ± 8.2 months after treatment initiation. For treated patients, average visual acuity (LogMAR) ± standard error of the mean improved from 0.5 ± 0.04 pre-treatment to 0.3 ± 0.1 at the second endpoint, 50.2 ± 7.3 months after treatment initiation.

Conclusions: Mild anatomic improvement of macular cysts was seen in pediatric patients using brinzolamide. Visual acuity improvement occurred even without significant reduction in macular cysts. Further studies are needed to determine whether the beneficial effects of carbonic anhydrase inhibitors are sustained in children with inherited retinal degenerations.     

Continued use of dorzolamide for the treatment of cystoid macular oedema in patients with retinitis pigmentosa

AIM: To determine the value of a topical carbonic anhydrase inhibitor for extended treatment of cystoid macular oedema (CME) in patients with retinitis pigmentosa (RP). METHOD: Eight patients with RP and foveal cystic-appearing lesions observed on fundus examination and by optical coherence tomography (OCT) testing were treated with a topical form of carbonic anhydrase inhibitor. RESULTS: Foveal cystic-like spaces were documented by OCT testing in all eight patients before treatment. All patients had a significant reduction in their foveal thickness (FT) and foveal zone thickness (FZT) in at least one eye after using 2% dorzolamide three times a day for 1 or 2 months. Six patients had an improvement in both eyes. After an additional 6-13 months of the same treatment regimen, out of six patients who had a sustained reduction in FT and FZT in at least one eye, four had this reduction in both eyes. While they were still taking Trusopt, a recurrence (rebound) of CME in both eyes was observed in two patients, whereas one patient had a sustained improvement in one eye and rebound of CME in the other eye. Out of 8 patients, 3 showed an improvement in their visual acuity by > or =7 letters, in at least one eye, on Snellen acuity charts, which was determined as clinically significant. CONCLUSION: Results from this study suggest that patients with RP could potentially sustain a beneficial effect from continued treatment with a topical form of carbonic anhydrase inhibitor.     

Rebound of cystoid macular edema with continued use of acetazolamide in patients with retinitis pigmentosa

PURPOSE: To demonstrate the presence of a rebound effect with the use of acetazolamide for the treatment of cystoid macular edema (CME) in patients with retinitis pigmentosa (RP). METHODS: Six patients with RP and cystic-appearing lesions in the macula demonstrated by fluorescein angiography and/or optical coherence tomography (OCT) were treated with an oral form of carbonic anhydrase inhibitor (acetazolamide [500 mg]) as a single daily dose. RESULTS: All patients, treated with acetazolamide for a period of 3 weeks to 5 weeks, had initial improvement of macular edema demonstrated by OCT. However, extended use of acetazolamide, for at least 8 weeks to 12 weeks, resulted in recurrence (rebound) of CME in 3 of the 6 patients. CONCLUSIONS: Results from our study suggest that rebound of CME with the continued use of acetazolamide observed by OCT may occur more frequently than previously appreciated.     

Antiretinal antibodies associated with cystoid macular edema

AIM: Recently, anti-Enolase and anti-carbonic anhydrase antibodies have been observed in over 60% of patients with retinitis pigmentosa (RP) and cystoid macular oedema (CME). We investigated the presence of these antibodies in a series of patients with CME due to different pathologies. METHODS: In 10 patients with CME serum antibodies against Carbonic anhydrase (CA) II (30 kD) and Enolase (46 kD) were sought using Western Blots, Dot Blots as well as ELISA. RESULTS: Western and dot blotting showed anti-CA II antibodies in all and anti-Enolase antibodies in six of the 10 patients. The average titer measured with ELISA was 0.9 +/- 0.08 OD Units (0.35-1.4) with a dilution of 1:400. CONCLUSION: The presence of anti-retinal antibodies in the serum of all patients confirms the high prevalence of these antibodies in patients with CME. This may suggest that a dysfunction of CA and enolase activity in the retinal pigment epithelium may lie at the root of oedema formation, whereas other mechanisms may be responsible in the absence of these antibodies.     

Bilateral disc edema and unilateral macular hole in a patient with retinitis pigmentosa

PURPOSE: A unique case of retinitis pigmentosa (RP) associated with bilateral disc edema and unilateral macular hole is presented. METHODS: A 49-year-old woman, a known RP patient, was found to have bilateral disc edema and a macular hole in the left eye during routine clinical examination. Fluorescein angiography revealed hyperfluorescent leakage of the optic nerve head significantly OD and minimally OS. There was staining in the macular regions which was consistent with retinal pigment epithelium atrophy OD and cystoid macular edema (CME) OS. Cerebrospinal fluid pressure and examination by lumbar puncture was normal. Disc edema spontaneously decreased bilaterally during follow-up. DISCUSSION: Bilateral disc edema was thought to be secondary to inflammation caused by rapid degeneration of photoreceptors and retinal pigment epithelium and macular hole was secondary to CME. CONCLUSIONS: Inflammatory response in the course of retinitis pigmentosa may result in disc edema and cystoid macular edema, which may further progresses to macular hole.     

Bilateral cystoid macular edema following successful treatment of AIDS-associated CMV retinitis

Background: Cystoid macular edema (CME) in AIDS patients with inactive cytomegalovirus (CMV) retinitis is an uncommon but potentially sight-threatening complication. The pathogenesis of CME in these patients is unclear. This study tries to identify possible risk factors by analyzing the charts of five patients. Methods: Ten eyes of 5 patients that finally developed CME were followed for an average of 18 months. The initial retinal lesions, their response to antiviral treatment, the development of CME, and the patients' immune status were prospectively monitored. Results: CMV retinitis was diagnosed at a median CD4+ count of 3 cells/mm³ (range 0–11). All eyes responded to the initial systemic anti-viral treatment. At the onset of CME, CMV retinitis was controlled by antiviral maintenance therapy in all patients [ganciclovir (n = 2), cidofovir (n = 2), foscarnet (n = 1)]. The median time between diagnosis of CMV retinitis and onset of CME was 11.5 months (range 5–24). Development of CME was associated with significant visual loss: acuity ranged from 0.05 to 0.7 when CME was first noticed, compared to 0.8–1.25 at diagnosis of CMV retinitis. Duration of inflammation, size or zone of retinal necrosis did not favor the development of CME, neither did the antiviral therapy. A weak correlation of CME development and immune status (expressed as increase of CD4+ cells) was found. Due to systemic corticosteroids CME resolved. Conclusions: CME is a new visual threat to AIDS-patients with CMV retinitis whose immune status improved under the latest combined antiretroviral therapy. Therapy with oral corticosteroids may positively influence this condition.      

The clinical efficacy of a topical dorzolamide in the management of cystoid macular edema in patients with retinitis pigmentosa

Background

Cystoid macular edema (CME) is one of the common complications of retinitis pigmentosa (RP), and is responsible for patient complications such as blurred and reduced visual acuity and for subsequent atrophic changes in the fovea. The objective of this work was to evaluate the clinical efficacy of a topical dorzolamide (a carbonic anhydrase inhibitor) in CME associated with RP.

Methods

Sixteen eyes of nine patients with CME secondary to typical forms of RP were included in the study. Baseline visual acuity, visual field, and optical coherence tomography (OCT) measurements were obtained for all patients. All patients used 1% dorzolamide three times daily in each eye. Patients underwent follow-up exams at 1, 3, and 6?months after treatment. The response to treatment was monitored by visual acuity and visual field measurement testing using the Humphrey Field Analyzer (HFA: the central 10-2 Program); in addition, foveal thickness was measured by OCT. Evaluation of macular sensitivity calculated by HFA as the average of 12 central points.

Results

Thirteen (81.3%) of 16 eyes showed a clear decrease in retinal thickness after treatment. Evaluation of macular sensitivity, calculated by HFA as the average of 12 central points (with the exception of foveal point data, showed an improvement of more than 1.0?dB in nine (56.3%) of 16 eyes. Moreover, both the mean deviation value and macular sensitivity were significantly improved. No severe side-effects were seen in any of the patients examined.

Conclusions

The results demonstrated that a topical dorzolamide is effective for the treatment of CME in patients with RP, and that the positive treatment effects last for up to 6?months.     

The Role of Fundus Autofluorescence in Late-Onset Retinitis Pigmentosa (LORP) Diagnosis

Abstract

Purpose: To demonstrate the utility and characteristics of fundus autofluorescence in late-onset retinitis pigmentosa.

Methods: Observational case series. Patients diagnosed with late-onset retinitis pigmentosa were identified retrospectively in an institutional setting. Twelve eyes of six patients were identified and medical records were reviewed.

Results: All patients presented with slowly progressive peripheral field loss and initial clinical examination revealed only subtle retinal changes. There was a notable lack of intraretinal pigment migration in all patients. Five out of six patients underwent magnetic resonance imaging of the brain to rule out intracranial processes and all were referred from another ophthalmologist for further evaluation. Fundus autofluorescence was ultimately employed in all patients and revealed more extensive retinal pathology than initially appreciated on clinical examination. Fundus autofluorescence directed the workup toward a retinal etiology in all cases and led to the eventual diagnosis of late-onset retinitis pigmentosa through electroretinogram testing.

Conclusion: Fundus autofluorescence may be a more sensitive marker for retinal pathology than stereo fundus biomicroscopy alone in late-onset retinitis pigmentosa. Early use of fundus autofluorescence imaging in the evaluation of patients with subtle retinal lesions and complaints of peripheral field loss may be an effective strategy for timely and cost-efficient diagnosis.     

CRB1: One Gene,Many Phenotypes

Abstract

Mutations in the CRB1 gene cause severe retinal degenerations, which may present as Leber congenital amaurosis, early onset retinal dystrophy, retinitis pigmentosa, or cone-rod dystrophy. Some clinical features should alert the ophthalmologist to the possibility of CRB1 disease. These features are nummular pigmentation of the retina, atrophic macula, retinal degeneration associated with Coats disease, and a unique form of retinitis pigmentosa named para-arteriolar preservation of the retinal pigment epithelium (PPRPE). Retinal degenerations associated with nanophthalmos and hyperopia, or with keratoconus, can serve as further clinical cues to mutations in CRB1. Despite this, no clear genotype-phenotype relationship has been established in CRB1 disease. In CRB1-disease, as in other inherited retinal degenerations (IRDs), it is essential to diagnose the specific disease-causing gene for the disease as genetic therapy has progressed considerably in the last few years and might be applicable.     

Nonclassic retinitis pigmentosa: A challenging clinical diagnosis solved by pedigree analysis and electrodiagnostic testing

PurposeThe aim of this study was to describe a case of nonclassic retinitis pigmentosa, to highlight ancillary testing tools for proper diagnosis, and to differentiate between common hereditary fundus dystrophies.MethodsMethods used in this study included complete ophthalmologic evaluation, optical coherence tomography, visual field testing, pedigree analysis, and electrodiagnostic testing.ResultsReduced vision and photopsia were the initial complaints of a patient who had an overall normal ocular appearance. However, a strong family history of retinitis pigmentosa and depressed scotopic and photopic electroretinograms confirmed the diagnosis of autosomal dominant retinitis pigmentosa.ConclusionIn cases of atypical-appearing retinitis pigmentosa, both pedigree analysis and electrodiagnostic testing are fundamental in correct diagnosis of this multifaceted hereditary fundus disorder.     

Inhibition of membrane-bound carbonic anhydrase enhances subretinal fluid absorption and retinal adhesiveness

· Background: The clinical use of currently available carbonic anhydrase (CA) inhibitors is limited by systemic side-effects, thought to result from the inhibition of intracellular CA isoenzymes. This study investigates how benzolamide, a carbonic anhydrase inhibitor which does not readily penetrate cell membranes, modulates retinal pigment epithelium functions relative to acetazolamide, which diffuses into the cytosol. · Methods: Small retinal detachments were made in Dutch rabbits by injecting saline into the subretinal space. Detachment height was measured using a dual He-Ne beam YAG laser focusing system, and the fluid absorption rate was calculated before and after intravenous injections of saline, acetazolamide or benzolamide. Retinal adhesiveness was determined by peeling the retina from the RPE and measuring the amount of adherent pigment. · Results: The baseline fluid absorption rate of 0.04 μl/mm²/h was unchanged after injection of 0.9% NaCl or low-dose benzolamide (5 mg/kg). The absorption increased to about 0.14 μl/mm²/h after higher benzolamide doses (20–40 mg/kg) and to 0.13 μl/mm²/h after acetazolamide (20 mg/kg). Both acetazolamide and benzolamide significantly slowed the post-enucleation failure of retinal adhesiveness. · Conclusion: Since benzolamide had effects similar to acetazolamide, inhibition of membrane-bound CA appears to be sufficient to enhance subretinal fluid absorption and retinal adhesiveness. Membrane-specific CA inhibitors may therefore be of clinical value if they minimize side-effects from intracellular CA inhibition. Received: 12 August 1998/Revised version received: 5 February 1999/Accepted: 30 March 1999     

Cystoid macular edema in a patient with acquired immunodeficiency syndrome and past ocular history of cytomegalovirus retinitis after initiation of protease inhibitors

Purpose: To describe a patient with acquired immunodeficiency syndrome (AIDS) who presented with cystoid macular edema (CME) which was not associated with active cytomegalovirus (CMV) retinitis or AIDS-related microvasculopathy. Method: A 32-year-old man with AIDS and a past ocular history of inactive CMV retinitis was placed on protease inhibitors when his CD4⁺ T lymphocyte counts dropped to 8 cells/mm³. Three months later, after his CD4⁺ T lymphocyte counts had increased to 196 cells/mm³ he complained of micropsia and metamorphopsia in his right eye of 1 week duration. The patient had a complete ocular examination including fluorescein angiography (FA). Results: Visual acuity (VA) was 7/10 OD. Fundus examination revealed CME and inactive CMV retinitis, and FA demonstrated CME and a hot disc. Two transseptal injections of corticosteroids were administered 2 weeks apart in the right eye as treatment of the CME. The patient reported gradual visual improvement and 6 weeks later, his VA was 10/10^-2. CME had resolved clinically and angiographically. Conclusions: CME in our case is associated with inactive CMV retinitis and gradually increasing number of CD4⁺ T lymphocytes after initiation of treatment with protease inhibitors. It may be amenable to regional administration of corticosteroids without reactivation of retinitis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Paradoxical response to carbonic anhydrase inhibitors in patients with intraretinal cystoid spaces

Background: Intraretinal cystoid spaces (IRCS) are fluid-filled spaces seen in some retinal dystrophies and often treated with carbonic anhydrase inhibitors. The purpose of this study is to report an unexpected bilateral improvement in the IRCS after discontinuation of therapy.

Material and Methods: We identified from our records 23 patients with retinal dystrophy and IRCS who had been treated with topical and/or oral carbonic anhydrase inhibitors. All subjects had regular follow-up with OCT and previous genetic testing.

Results: We identified four (17%) patients who experienced a bilateral and symmetrical paradoxical improvement in IRCS size and visual acuity after discontinuation of carbonic anhydrase inhibitors. Two were mutations in RS1, one in CLN3 and another in NR2E3. All patients were followed for at least three years (range 39–63 months). None had systemic abnormalities.

Conclusions: Patients with IRCS may exhibit a paradoxical response after discontinuation of carbonic anhydrase inhibitors. Although the pathophysiology of these phenomena is unclear, stopping treatment may be an option in patients who cease to improve or get worse on treatment.     

Cystoid macular edema following immune recovery and treatment with cidofovir for cytomegalovirus retinitis

· Background: Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection in AIDS patients. Cidofovir has proved to be highly effective in treatment of CMV retinitis. Iritis and bulbar hypotony are known as the major complications after intravenous and intravitreal use of this antiviral drug. Cystoid macular edema (CME) after intravenous application of cidofovir has not been reported. · Methods: We analyzed retrospectively the incidence of CME after intravitreal or intravenous application of cidofovir and its correlation with CD4 cell counts of the patients. · Results: Two (22.2%) of 9 eyes in the intravenous and 3 (18.8%) of 16 eyes in the intravitreal injection group developed CME. It occurred between 3 and 48 weeks after cidofovir administration. In all eyes CMV retinitis was inactive. All patients received highly active antiretroviral treatment (HAART). CME was correlated with a rapid and sustained improvement in CD4 cell counts. · Conclusion: We interpret the occurrence of CME as an immune recovery phenomenon for the following reasons. All CMEs were seen in eyes with inactive CMV retinitis and the unaffected contralateral side never developed CME. The time range of appearance between 3 and 48 weeks after cidofovir administration makes direct toxicity of cidofovir unlikely. All patients had a sustained improvement of CD4 cell counts due to HAART. No CME was reported during the use of cidofovir before the HAART era. Received: 22 December 1998 Revised version received: 3 March 1999 Accepted: 30 March 1999     

Acuity recovery and cone pigment regeneration after a bleach in patients with retinitis pigmentosa and rhodopsin mutations.

PURPOSE: To assess visual acuity recovery times and cone photopigment regeneration kinetics after a bleach in the fovea of patients with dominant retinitis pigmentosa due to rhodopsin mutations. METHODS: The authors measured acuity recovery times by computerized photostress testing in 13 patients with dominant retinitis pigmentosa and one of eight rhodopsin mutations. The authors also measured their time constants of cone photopigment regeneration with a video imaging fundus reflectometer to determine whether acuity recovery time depended on pigment regeneration kinetics. These values were compared with those of normal subjects, by the Mann-Whitney U test. The relationship between acuity recovery time and the time constant of cone photopigment regeneration among the patients was quantified by the Spearman rank correlation. RESULTS: The visual acuity recovery times, which averaged 22.0 seconds for the patients with retinitis pigmentosa and 11.2 seconds for the normal subjects, were significantly slower for the patient group (P < 0.001). The time constants of cone pigment regeneration, which averaged 172 seconds for the patients with retinitis pigmentosa and 118 seconds for the normal subjects, also were significantly slower for the patient group (P = 0.043). The authors also found a significant, positive correlation between the visual acuity recovery time and the time constant of pigment regeneration for the patients with retinitis pigmentosa (r = 0.65, P = 0.017). CONCLUSIONS: A slowing of foveal visual acuity recovery and cone pigment regeneration, which are related to each other, can occur in patients with retinitis pigmentosa, due to a rod-specific gene defect.     

Adult cytomegalic inclusion retinitis.

Two cases of adult cytomegalic inclusion retinitis are described in renal transplant patients. The areas of initial involvement by the retinitis were left atrophic and demarcated from normal retina by a hypopigmented area in the retina. Both cases were complicated by the development of a secondary glaucoma with open angles. The glaucoma in each patient was successfully managed by carbonic anhydrase inhibitors, epinephrine drops, and cycloplegias. One patient still retains normal visual acuity in the eye which had active retinitis.     

Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).

Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.

Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.

Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa.