Hydroxychloroquine retinopathy.

Hydroxychloroquine (HCQ; Plaquenil) is used increasingly in the management of a variety of autoimmune disorders, with well established roles in dermatology and rheumatology and emerging roles in oncology. Hydroxychloroquine has demonstrated a survival benefit in patients with systemic lupus erythematosus; some clinicians advocate its use in all such patients. However, Hydroxychloroquine and chloroquine (CQ) have been associated with irreversible visual loss due to retinal toxicity. Hydroxychloroquine retinal toxicity is far more common than previously considered; an overall prevalence of 7.5% was identified in patients taking HCQ for greater than 5 years, rising to almost 20% after 20 years of treatment. This review aims to provide an update on HCQ/CQ retinopathy. We summarise emerging treatment indications and evidence of efficacy in systemic disease, risk factors for retinopathy, prevalence among HCQ users, diagnostic tests, and management of HCQ retinopathy. We highlight emerging risk factors such as tamoxifen use, and new guidance on safe dosing, reversing the previous recommendation to use ideal body weight, rather than actual body weight. We summarise uncertainties and the recommendations made by existing HCQ screening programmes. Asian patients with HCQ retinopathy may demonstrate an extramacular or pericentral pattern of disease; visual field testing and retinal imaging should include a wider field for screening in this group. HCQ is generally safe and effective for the treatment of systemic disease but because of the risk of HCQ retinal toxicity, modern screening methods and ideal dosing should be implemented. Guidelines regarding optimal dosing and screening regarding HCQ need to be more widely disseminated.

Fundus autofluorescence imaging: systematic review of test accuracy for the diagnosis and monitoring of retinal conditions.

We conducted a systematic review of the accuracy of fundus autofluorescence (FAF) imaging for diagnosing and monitoring retinal conditions. Searches in November 2014 identified English language references. Sources included MEDLINE, EMBASE, the Cochrane Library, Web of Science, and MEDION databases; reference lists of retrieved studies; and internet pages of relevant organisations, meetings, and trial registries. For inclusion, studies had to report FAF imaging accuracy quantitatively. Studies were critically appraised using QUADAS risk of bias criteria. Two reviewers conducted all review steps. From 2240 unique references identified, eight primary research studies met the inclusion criteria. These investigated diagnostic accuracy of FAF imaging for choroidal neovascularisation (one study), reticular pseudodrusen (three studies), cystoid macular oedema (two studies), and diabetic macular oedema (two studies). Diagnostic sensitivity of FAF imaging ranged from 32 to 100% and specificity from 34 to 100%. However, owing to methodological limitations, including high and/or unclear risks of bias, none of these studies provides conclusive evidence of the diagnostic accuracy of FAF imaging. Study heterogeneity precluded meta-analysis. In most studies, the patient spectrum was not reflective of those who would present in clinical practice and no studies adequately reported whether FAF images were interpreted consistently. No studies of monitoring accuracy were identified. An update in October 2016, based on MEDLINE and internet searches, identified four new studies but did not alter our conclusions. Robust quantitative evidence on the accuracy of FAF imaging and how FAF images are interpreted is lacking. We provide recommendations to address this.

Hydroxychloroquine retinopathy: an emerging problem.

PurposeThe aim of this case series is to raise awareness of the emerging issue of serious retinal damage caused by the prolonged use of hydroxychloroquine (HCQ) and the importance of adequate and appropriate monitoring of visual function during treatment.Patient and methodsThis is a small retrospective case series of 3 patients on long-term HCQ who developed serious symptomatic retinal toxicity confirmed on imaging and functional testing.ResultsAll 3 patients were treated with HCQ for over 15 years; two for rheumatoid arthritis (RA), and the third for systemic lupus erythematosus (SLE). All 3 patients had macular involvement varying in severity confirmed with characteristic features on imaging and functional testing (Optical Coherence Tomography (OCT), Autofluorescence (AF) and Humphrey 10-2 visual fields).ConclusionHCQ is widely used to treat autoimmune conditions with a proven survival benefit in patients with SLE. However, long-term use can be associated with irreversible retinal toxicity. These cases highlight that HCQ, like chloroquine, can also cause visual loss in susceptible individuals. Early detection of presymptomatic retinal changes by the introduction of appropriate screening and monitoring is mandatory to limit the extent of irreversible visual loss due to HCQ retinal toxicity.

Ultraviolet or blue-filtering intraocular lenses: what is the evidence?

Cataract surgery was revolutionised by the introduction of modern intraocular lenses in the late 1940's. By the late 1960's to 1970's evidence had emerged that short-wavelength light caused phototoxicity at the retina and retinal pigment epithelium. By the early 1980's ultraviolet filters had been incorporated into intraocular lenses. This caused intense controversy, as there was concern that the UV-filtering chromophore might leach out into the eye causing toxicity. With the arrival of blue-filtering intraocular lenses (BFIOLs) in 1990's, a further debate was ignited as to their safety and potential disadvantages. Selecting the optimal performing intraocular lens to obtain the best visual performance with the fewest potential drawbacks has become complex and challenging for cataract surgeons and their patients with the wide choice of lenses available. Choosing a personalised lens to address astigmatism, presbyopia, spherical aberration, chromatic aberration, and potentially to shield the retina from short-wavelength light is now possible. The potential benefits and possible side effects of these different innovations emphasise the importance of assessing the evidence for their clinical utility, allowing the surgeon and the patient to weigh-up the risk benefit ratio and make an informed decision. The BFIOLs were developed to reduce cyanopsia, address chromatic aberration, and improve contrast sensitivity in different lighting conditions, as well as to prevent short-wavelength light reaching the retina thus potentially reducing the risk of developing age-related macular degeneration. Further design development of the BFIOLs was to mimic the natural crystalline lens absorption and transmittance properties in adulthood. Multiple publications have reported on the potential benefits and pitfalls of implanting a blue-filtering lens. The potential disadvantages raised in the literature over the last 25 years since their introduction, regarding compromise of visual function and disruption of the circadian system, have been largely dispelled. The clear benefits of protecting the retina from short-wavelength light make a BFIOLs a sensible choice. The purpose of this article presented at the Cambridge symposium 2015 is to review the literature on this subject.

Colour photographs for screening in neovascular age-related macular degeneration: are they necessary?

AIMS: To investigate whether optical coherence tomography (OCT) with associated infra-red images provide enough information to determine treatment decisions in the management of neovascular age-related macular degeneration (nAMD), or whether retinal colour photography is also necessary. METHODS: In all, 87 OCT scans of 82 eyes with nAMD undergoing monitoring post ranibizumab treatment were taken using the Zeiss Stratus (Carl Zeiss Meditec, Jena, Germany; n=87) together with their corresponding infra-red images. Fundus colour photographs were also taken. These images were reviewed by an experienced assessor, and a ranibizumab treatment decision was made during a multidisciplinary team retinal image review meeting. RESULTS: In all, 30 OCT scans (34.5%) showed intraretinal or subretinal oedema. A total of 24 colour photographs (19.5%) demonstrated retinal haemorrhage. Corresponding OCT infra-red images gave poor sensitivity in detecting haemorrhages (0.176). In 16.7% of decisions to treat, haemorrhage alone was the deciding factor. Signs of disease activity seen only on colour photography were the deciding factor in clinical decisions for 8% of scans assessed. CONCLUSIONS: The presence or increase of intra-retinal oedema is an important sign of activity triggering ranibizumab retreatment, but some eyes show signs of retinal haemorrhage without coexisting oedema. These haemorrhages are often only seen on either colour imaging or fundoscopy and are unclear or invisible on OCT scans and infra-red images. Therefore, although retinal colour photography creates additional expense, it is indispensable for making informed retreatment decisions, if patients are monitored using retinal imaging alone.

Autosomal dominant cone-rod dystrophy with mutations in the guanylate cyclase 2D gene encoding retinal guanylate cyclase-1.

OBJECTIVE: To describe the phenotype in 4 families with dominantly inherited cone-rod dystrophy, 1 with an R838C mutation and 1 with an R838H mutation in the guanylate cyclase 2D (GUCY2D) gene encoding retinal guanylate cyclase-1. METHODS: Psychophysical and electrophysiological evaluation and confocal laser scanning ophthalmoscopic imaging was performed on 10 affected members of 4 British families. RESULTS: Although subjects had lifelong poor vision in bright light, a major reduction in visual acuity did not occur in most of them until after their late teens. Fundus abnormalities were confined to the central macula, and increasing central atrophy was noted with age. Increased background autofluorescence was observed surrounding the central atrophic area. Electrophysiological testing revealed a marked loss of cone function with only minimal rod involvement, even in older subjects. Photopic and scotopic static perimetry demonstrated central and peripheral cone-mediated threshold elevations with midperipheral sparing. CONCLUSION: The phenotype associated with autosomal dominant cone-rod dystrophy with either an R838C or R838H mutation in GUCY2D is distinctive, with predominantly cone system involvement. There is some variation in severity within the 3 families with the R838C mutation. CLINICAL RELEVANCE: Families with the R838C or R838H mutation have a much milder phenotype than the family previously described that had 2 sequence changes, E837D and R838S, in GUCY2D.

Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1.

OBJECTIVE: To describe the phenotype in 3 families with dominantly inherited cone and cone-rod dystrophy with mutations in guanylate cyclase activator 1A (GUCA1A), the gene-encoding guanylate cyclase activator protein-1 (GCAP-1). METHODS: Phenotypic characterization with psychophysical and electrophysiological evaluation and confocal laser scanning ophthalmoscopy was performed in 2 families with a Tyr99Cys mutation and 1 family with a Pro50Leu mutation. Haplotype analysis was performed in the families with Tyr99Cys mutation. RESULTS: The families with a Y99C mutation were shown to be ancestrally related. Decreased visual acuity and loss of color vision occurred after the age of 20 years, followed by progressive atrophy of the central 5 degrees to 10 degrees. Electrophysiological testing revealed generalized loss of cone function, with preservation of rod function. Abnormal rod and cone sensitivities were confined to the central 5 degrees to 10 degrees. Confocal laser scanning ophthalmoscopy imaging showed abnormalities of autofluorescence in early disease. Subjects with a Pro50Leu mutation demonstrated marked variability in expressivity from minimal abnormalities of macular function to cone-rod dystrophy. CONCLUSIONS: The phenotype associated with the Y99C mutation in GUCA1A is distinctive, with little variation in expression. By contrast, that associated with the P50L mutation demonstrates variable expressivity. CLINICAL RELEVANCE: Phenotype-genotype correlation in these 2 mutations demonstrates 2 different phenotypes.

Ophthalmologists' perspective.

Molecular biology has significantly contributed to our understanding of inherited retinal disease, in particular to that of monogenic disorders. The discovery of the responsible gene, the elucidation of its function, and the increasing understanding of the pathogenesis of inherited retinal disorders is both exciting and important. From the clinician's point of view, this new information is helpful in diagnosis and prognosis, and may ultimately yield benefits in the form of therapy. This chapter deals with the advances made in the field of molecular biology as it pertains to inherited retinal disorders from the perspective of the clinician. Identification of specific loci, genes, and causative mutations have led to reclassification and reordering of the preexisting nosological classification. Progression in the understanding of the function of the relevant protein, and putative metabolic disturbance caused by the mutation at the cellular level, is continuing and therapies developed to address these abnormalities are currently undergoing evaluation.