***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Purpose Centripetal retinal degeneration in choroideremia ( CHM ) leads to early visual field restriction and late central vision loss . The latter marks an acute decline in quality of life but visual prognostication remains challenging . We investigated visual function in CHM by correlating best-corrected visual acuity ( BCVA ) , microperimetry and multimodal imaging . Methods Fifty-six consecutive CHM patients attending Oxford Eye Hospital were examined with  BCVA , 10–2 microperimetry , optical coherence tomography , and fundus autofluorescence ( AF ) . Microperimetry was repeated in 21 eyes and analyzed with Bl and -Altman . Kaplan-Meier survival plots of eyes retaining 20/20 BCVA were created . Intereye symmetry was assessed . Results Microperimetry coefficient of repeatability was 1.45 dB. Survival analysis showed an indistinguishable pattern between eyes ( median survival 39 years ) . Macular sensitivity showed a similar decline in right and left eyes , with half-lives of 13.6 years . Zonal analysis showed faster decline nasal to the fovea . Intereye symmetry was more consistent for microperimetry sensitivity ( r = 0.95 , P < 0.001 ) than BCVA ( r = 0.42 , P = 0.0006 ) . Near normal foveal sensitivity was maintained when the fovea was at least 2500 μm from the advancing edge of AF . Conclusions BCVA is a marker of central degeneration and can provide valuable information about the position of the remaining retina as well as a measure of the impact on daily living . Microperimetry represents the global macular region . Both visual functions showed a high degree of intereye symmetry , particularly in early stages , indicating the fellow eye can provide a suitable control for assessing interventions to one eye . The findings may help to tailor visual prognosis and interpret outcomes of trials Summary Background Choroideremia is an X-linked recessive disease that leads to blindness due to mutations in the CHM gene , which encodes the Rab escort protein 1 ( REP1 ) . We assessed the effects of retinal gene therapy with an adeno-associated viral ( AAV ) vector encoding REP1 ( AAV.REP1 ) in patients with this disease . Methods In a multicentre clinical trial , six male patients ( aged 35–63 years ) with choroideremia were administered AAV.REP1 ( 0·6–1·0 × 1010 genome particles , subfoveal injection ) . Visual function tests included best corrected visual acuity , microperimetry , and retinal sensitivity tests for comparison of baseline values with 6 months after surgery . This study is registered with Clinical Trials.gov , number NCT01461213 . Findings Despite undergoing retinal detachment , which normally reduces vision , two patients with advanced choroideremia who had low baseline best corrected visual acuity gained 21 letters and 11 letters ( more than two and four lines of vision ) . Four other patients with near normal best corrected visual acuity at baseline recovered to within one to three letters . Mean gain in visual acuity overall was 3·8 letters ( SE 4·1 ) . Maximal sensitivity measured with dark-adapted microperimetry increased in the treated eyes from 23·0 dB ( SE 1·1 ) at baseline to 25·3 dB ( 1·3 ) after treatment ( increase 2·3 dB [ 95 % CI 0·8–3·8 ] ) . In all patients , over the 6 months , the increase in retinal sensitivity in the treated eyes ( mean 1·7 [ SE 1·0 ] ) was correlated with the vector dose administered per mm2 of surviving retina ( r=0·82 , p=0·04 ) . By contrast , small non-significant reductions ( p>0·05 ) were noted in the control eyes in both maximal sensitivity ( –0·8 dB [ 1·5 ] ) and mean sensitivity ( –1·6 dB [ 0·9 ] ) . One patient in whom the vector was not administered to the fovea re-established variable eccentric fixation that included the ectopic isl and of surviving retinal pigment epithelium that had been exposed to vector . Interpretation The initial results of this retinal gene therapy trial are consistent with improved rod and cone function that overcome any negative effects of retinal detachment . These findings lend support to further assessment of gene therapy in the treatment of choroideremia and other diseases , such as age-related macular degeneration , for which intervention should ideally be applied before the onset of retinal thinning . Funding UK Department of Health and Wellcome Trust In genetic disorders associated with premature neuronal death , symptoms may not appear for years or decades . This delay in clinical onset is often assumed to reflect the occurrence of age-dependent cumulative damage . For example , it has been suggested that oxidative stress disrupts metabolism in neurological degenerative disorders by the cumulative damage of essential macromolecules . A prediction of the cumulative damage hypothesis is that the probability of cell death will increase over time . Here we show in contrast that the kinetics of neuronal death in 12 models of photoreceptor degeneration , hippocampal neurons undergoing excitotoxic cell death , a mouse model of cerebellar degeneration and Parkinson 's and Huntington 's diseases are all exponential and better explained by mathematical models in which the risk of cell death remains constant or decreases exponentially with age . These kinetics argue against the cumulative damage hypothesis ; instead , the time of death of any neuron is r and om . Our findings are most simply accommo date d by a ‘ one-hit ’ biochemical model in which mutation imposes a mutant steady state on the neuron and a single event r and omly initiates cell death . This model appears to be common to many forms of neurodegeneration and has implication s for therapeutic strategies Purpose We set out to characterize the pattern of fundus autofluorescence ( AF ) loss in choroideremia ( CHM ) patients of varying ages and disease severity in order to determine the average rate of progression of this potential disease biomarker . Methods Fifty consecutive CHM patients ( 100 eyes ) attending outpatient clinics at Oxford Eye Hospital underwent analysis with the Heidelberg OCT Spectralis with autofluorescence capabilities .  The area of residual AF was traced using Heidelberg Eye Explorer . Bl and -Altman analysis was used to calculate the coefficient of repeatability ( CR ) . The degree of AF loss was correlated to different ages and the pattern of residual AF constructed into color-coded maps in order to gain insight into the mechanism of disease progression . Results The CR for measurement of AF area is < 1 % , indicating that a small change is likely to be significant . Correlation of patient age and area of residual AF produced a clinical ly relevant index of expected anatomic disease . Progression is 7.7 % of the residual area each year ( 95 % confidence intervals 7.0%–8.2 % ) and follows a logarithmic pattern with age ( r = 0.95 , P < 0.001 ) . From this we derived the mean half-life of AF as 9 years . Qualitatively , the pattern of remaining AF centered on a point temporal to the fovea . Conclusions The area of residual AF in CHM can be measured reproducibly and shows a distinct pattern of loss . The measured residual area is inversely correlated to age . The ratio of the two variables may provide useful information regarding the rate of progression for any one individual at a given point in time Choroideremia is an incurable X-linked retinal degeneration caused by mutations in the gene encoding Rab escort protein-1 . A group of clinical ly defined and genotyped patients were studied to determine : ( 1 ) the degree of rod and cone dysfunction and structural abnormality in the central retina and the level of macular pigment ; and ( 2 ) the response of macular pigment and foveal vision to a 6 month trial of supplementation with oral lutein ( at 20 mg per day ) . Rod and cone-mediated function was measured with dark-adapted static perimetry ; in vivo retinal structure was determined with optical coherence tomography ; and macular pigment optical density was measured with heterochromatic flicker photometry . In this cohort of patients ( ages 15 - 65 years ) , both rod- and cone-mediated central function declined with age as did central retinal thickness . Macular pigment levels did not differ between patients and male control subjects . Supplementation of oral lutein in a subset of patients led to an increase in serum lutein and macular pigment levels ; absolute foveal sensitivity did not change . It is concluded that macular pigment density can be augmented by oral intake of lutein in patients with choroideremia . There was no short-term change in the central vision of the patients on the supplement , but long-term influences of lutein supplementation on disease natural history warrant further study Purpose We report the underlying genotype and explore possible genotypic-phenotypic correlations in a large cohort of choroideremia patients . Methods We studied prospect ively a cohort of 79 patients diagnosed within a tertiary referral service for patients with retinal dystrophies . Phenotypic evaluation consisted of clinical examination , including visual acuity and residual retinal area by  fundus autofluorescence  ( FAF ) . Genotype was established by sequencing . We also investigated whether particular genotypes were associated with more severe phenotypes by performing analysis of covariance ( ANCOVA ) , with visual acuity and FAF as the dependent variables and age as the covariant . Results A total of 74 ( 94 % ) of patients in our cohort had causative mutations by sequencing , the majority of which were anticipated to be null . Of these , 35 ( 47 % ) had insertions and deletions , 13 ( 18 % ) had mutations predicted to affect splicing , and 26 ( 35 % ) had single point mutations . In the latter case , 13 of 21 ( 62 % ) pedigrees with single point mutations were C to T transitions at C-phosphate-G ( CpG ) dinucleotides . These mutations were spread across 5 of only 24 CpG dinucleotides in the entire CHM cDNA . Furthermore , these 5 locations are the only sites at which C to T transitions result in a stop codon . No clear evidence was found for genotype – phenotype correlation except in the instance of a patient with a large deletion involving neighbouring sequences . Conclusions In patients with a diagnosis of choroideremia made by a specialty service , there is a high likelihood of establishing a genetic diagnosis . The majority of causative mutations appear to be null and , therefore , may benefit from gene replacement therapy . A disproportionate number of single point mutations observed were C to T transitions , consistent with the evolutionary decay of CpG dinucleotides through methylation and subsequent deamination . Hence , the development of choroideremia in such patients may represent the unwanted consequence of human evolution ; de novo mutations are predicted to arise at these sites in future generations . ( Clinical Trials.gov number , NCT01461213 . PURPOSE To determine whether emixustat hydrochloride ( emixustat ) reduces the rate of enlargement of geographic atrophy ( GA ) compared with placebo in subjects with age-related macular degeneration ( AMD ) and to evaluate the safety and tolerability of emixustat over 24 months of treatment . DESIGN Multicenter , r and omized , double-masked , placebo-controlled , phase 2b/3 clinical trial . PARTICIPANTS Patients with GA secondary to AMD , a visual acuity score of at least 35 letters , and GA with a total area of 1.25 to 18 mm2 were enrolled . METHODS Subjects were r and omized ( 1:1:1:1 ) to emixustat 2.5 mg , 5 mg , 10 mg , or placebo , administered orally once daily for 24 months . Visits included screening , baseline , and months 1 , 2 , 3 , 6 , 9 , 12 , 15 , 18 , 21 , 24 , and 25 . MAIN OUTCOME MEASURES The primary efficacy end point was the mean annual growth rate of total GA area in the study eye , as measured by a central reading center using fundus autofluorescence ( FAF ) images . The change from baseline in normal luminance best-corrected visual acuity ( NL-BCVA ) was a secondary efficacy end point . RESULTS Of 508 r and omized subjects , 320 completed the study . Demographics and baseline characteristics were comparable between treatment groups . On average , GA lesions in the study eye grew at a similar rate in each group ( emixustat : 1.69 to 1.84 mm2/year ; placebo : 1.69 mm2/year ; P ≥ 0.81 ) . Changes in NL-BCVA were also comparable between groups . Subjects with a larger low luminance deficit ( LLD ) at baseline ( ≥20 letters ) demonstrated a more rapid growth of GA over 24 months . No relationship was observed between the risk-allele status of the AMD-associated single-nucleotide polymorphisms tested and the growth rate of GA . The most common adverse events in emixustat-treated subjects were delayed dark adaptation ( 55 % ) , chromatopsia ( 18 % ) , visual impairment ( 15 % ) , and erythropsia ( 15 % ) . CONCLUSIONS Emixustat did not reduce the growth rate of GA in AMD . The most common adverse events were ocular in nature and likely related to the drug 's mechanism of action . Data gained from this study over a 2-year period add to the underst and ing of the natural history of GA and the baseline characteristics affecting the growth rate of GA Purpose The purpose of this study was to investigate fundus autofluoresc 
    Output:
    
The loss of residual RPE area in untreated eyes with CHM follows the AEM over approximately 60 years .
Log-transformed residual RPE area measured by FAF can serve as an anatomic endpoint to monitor CHM