RESUMO
Posterior microphthalmos (MCOP) is a rare isolated developmental anomaly of the eye characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal-recessive form (arMCOP) of the disease. Based on published linkage data, we refined the position of the disease locus (MCOP6) in an interval of 250 kb in chromosome 2q37.1 in two large Faroese families. We detected three different mutations in PRSS56. Patients of the Faroese families were either homozygous for c.926G>C (p.Trp309Ser) or compound heterozygous for c.926G>C and c.526C>G (p.Arg176Gly), whereas a homozygous 1 bp duplication (c.1066dupC) was identified in five patients with arMCOP from a consanguineous Tunisian family. In one patient with MCOP from the Faroe Islands and in another one from Turkey, no PRSS56 mutation was detected, suggesting nonallelic heterogeneity of the trait. Using RT-PCR, PRSS56 transcripts were detected in samples derived from the human adult retina, cornea, sclera, and optic nerve. The expression of the mouse ortholog could be first detected in the eye at E17 and was maintained into adulthood. The predicted PRSS56 protein is a 603 amino acid long secreted trypsin-like serine peptidase. The c.1066dupC is likely to result in a functional null allele, whereas the two point mutations predict the replacement of evolutionary conserved and functionally important residues. Molecular modeling of the p.Trp309Ser mutant suggests that both the affinity and reactivity of the enzyme toward in vivo protein substrates are likely to be substantially reduced.
Assuntos
Genes Recessivos/genética , Microftalmia/genética , Mutação/genética , Serina Endopeptidases/genética , Serina Proteases/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Análise Mutacional de DNA , Olho/enzimologia , Olho/patologia , Família , Regulação Enzimológica da Expressão Gênica , Loci Gênicos/genética , Humanos , Meiose/genética , Camundongos , Microftalmia/enzimologia , Modelos Moleculares , Dados de Sequência Molecular , Serina Endopeptidases/química , Serina Endopeptidases/metabolismo , Serina Proteases/química , Serina Proteases/metabolismoRESUMO
OBJECTIVE: To investigate the visual outcome, pattern of discontinuation, ocular complications, and mortality of patients treated with a variable ranibizumab dosing regimen for neovascular age-related macular degeneration (AMD) for 4 years. DESIGN: Retrospective chart review supplemented with clinical examination. PARTICIPANTS: Six hundred eyes of 555 patients initiated intravitreal treatment with vascular endothelial growth factor inhibition for neovascular AMD in 2007 in a community-based hospital. METHODS: Patient data from a database were retrieved from 2007 through 2011. Descriptive evaluation of the main outcome measures was carried out for the cohort of patients. A group of patients who had been discontinued because of apparent disease inactivity was reexamined. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA; Snellen), number of intravitreal injections, causes of discontinuations, ocular complications, and standardized mortality rate. RESULTS: One hundred ninety-two eyes (32%) were still receiving active treatment after 4 years. The mean BCVA in the 192 eyes was unchanged from the start (baseline, 0.30; 4-year follow-up, 0.32; P>0.3). Visual acuity after the third loading dose was associated significantly with the outcome (P<0.0001) and was a better predictor than baseline acuity. The mean number of injections was 5.5 per year. For 408 eyes (68%), discontinuation of treatment was motivated by the following 4 reasons: lack of apparent treatment response (28%), failure to appear at follow-up (11%), death (9%), and disease inactivity (20%, 120 eyes). Treatment was resumed later in 18% of patients discontinued because of inactivity. Sixty-seven eyes were reexamined in 2012 from the group of patients with disease inactivity. The final visual acuity by then had decreased significantly from the time of discontinuation, from 0.38 to 0.15 (P = 0.001). Endophthalmitis occurred in 2 eyes of 7584 injections. A total of 125 patients had died, corresponding to 75% of the mean mortality in the community. CONCLUSIONS: One third of the eyes were still receiving active treatment after 4 years and had stable visual acuity. One third of fellow eyes (eyes at risk) started treatment during the 4 years. One fifth of discontinued eyes resumed treatment, indicating that close follow-up should be maintained for patients discontinued because of disease inactivity. The ocular complication rate was 0.2%, and the mortality rate was below expected.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais Comunitários , Humanos , Injeções Intravítreas , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ranibizumab , Retratamento , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/mortalidade , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
PURPOSE: To report the effect of anti-vascular endothelial growth factor inhibitor (anti-VEGF) on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy. METHODS: A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema and optic disc edem a. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29. RESULTS: The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone and subtenonal kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal VEGF inhibitor injection therapy. The anti-VEGF therapy diminished cystoid macular edema in the fovea and improved the visual acuity. CONCLUSION: Here we report for the first time the long-term outcomes of anti-VEGF injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.
RESUMO
PURPOSE: In this study, we investigate the potential of a novel artificial intelligence-based system for autonomous follow-up of patients treated for neovascular age-related macular degeneration (AMD). METHODS: A temporal deep learning model was trained on a data set of 84 489 optical coherence tomography scans from AMD patients to recognize disease activity, and its performance was compared with a published non-temporal model trained on the same data (Acta Ophthalmol, 2021). An autonomous follow-up system was created by augmenting the AI model with deterministic logic to suggest treatment according to the observe-and-plan regimen. To validate the AI-based system, a data set comprising clinical decisions and imaging data from 200 follow-up consultations was collected prospectively. In each case, both the autonomous AI decision and original clinical decision were compared with an expert panel consensus. RESULTS: The temporal AI model proved superior at detecting disease activity compared with the model without temporal input (area under the curve 0.900 (95% CI 0.894-0.906) and 0.857 (95% CI 0.846-0.867) respectively). The AI-based follow-up system could make an autonomous decision in 73% of the cases, 91.8% of which were in agreement with expert consensus. This was on par with the 87.7% agreement rate between decisions made in the clinic and expert consensus (p = 0.33). CONCLUSIONS: The proposed autonomous follow-up system was shown to be safe and compliant with expert consensus on par with clinical practice. The system could in the future ease the pressure on public ophthalmology services from an increasing number of AMD patients.
Assuntos
Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Inteligência Artificial , Seguimentos , Degeneração Macular/diagnóstico , Tomografia de Coerência Óptica/métodos , Consenso , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológicoRESUMO
PURPOSE: To meet the demands imposed by the continuing growth of the Age-related macular degeneration (AMD) patient population, automation of follow-ups by detecting retinal oedema using deep learning might be a viable approach. However, preparing and labelling data for training is time consuming. In this study, we investigate the feasibility of training a convolutional neural network (CNN) to accurately detect retinal oedema on optical coherence tomography (OCT) images of AMD patients with labels derived directly from clinical treatment decisions, without extensive preprocessing or relabelling. METHODS: A total of 50 439 OCT images with associated treatment information were retrieved from databases at the Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark between 01.06.2007 and 01.06.2018. A CNN was trained on the retrieved data with the recorded treatment decisions as labels and validated on a subset of the data relabelled by three ophthalmologists to denote presence of oedema. RESULTS: Moderate inter-grader agreement on presence of oedema in the relabelled data was found (76.4%). Despite different training and validation labels, the CNN performed on par with inter-grader agreement in detecting oedema on OCT images (AUC 0.97, accuracy 90.9%) and previously published models based on relabelled datasets. CONCLUSION: The level of performance shown by the current model might make it valuable in detecting disease activity in automated AMD patient follow-up systems. Our approach demonstrates that high accuracy is not necessarily constrained by incongruent training and validation labels. These results might encourage the use of existing clinical databases for development of deep learning based algorithms without labour-intensive preprocessing in the future.
Assuntos
Algoritmos , Aprendizado Profundo , Educação de Pós-Graduação em Medicina/métodos , Degeneração Macular/complicações , Edema Macular/diagnóstico , Oftalmologistas/educação , Tomografia de Coerência Óptica/métodos , Feminino , Seguimentos , Humanos , Macula Lutea/diagnóstico por imagem , Degeneração Macular/diagnóstico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos RetrospectivosRESUMO
Intravitreal injections with vascular endothelial growth factor inhibitors constitute the most prevalent ophthalmic procedure in developed countries. Historically, there has been steady growth in the number of treatments performed of this kind, and projection studies estimate further growth in such treatments in the future. We provide a practical approach to intravitreal injections and discuss important aspects relating to the setting, the patient, the procedure, and the information given to the patient.
RESUMO
PURPOSE: To study visual outcome and number of annual injections in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) before and after a change in first-line therapy from ranibizumab to aflibercept in a high-volume clinical practice. METHODS: This was a retrospective chart review of routine clinical practice. The study included 1027 treatment-naïve patients, 559 of whom started intravitreal ranibizumab therapy in 2011-2012 and 468 of whom started intravitreal aflibercept therapy in 2013-2014, a fixed loading dose of three injections followed by a pro re nata treatment regimen used in both periods. RESULTS: Snellen best-corrected visual acuity (BCVA) at baseline and after one year was 0.23 and 0.31 (p < 0.0001), respectively, for patients treated with ranibizumab and 0.25 and 0.33 (p < 0.0001) for patients treated with aflibercept, last observation carried forward. The share of patients (73%) still in treatment with ranibizumab at year 1 had a baseline BCVA of 0.26 but 0.40 at year 1 (p < 0.0001), and the patients (75%) still in treatment with aflibercept at year 1 had a baseline BCVA of 0.28 but 0.42 at year 1 (p < 0.0001). Proportional visual gains for both cohorts were comparable for one year (p = 0.14). The number of injections given within year 1 including first injection was 6.9 for ranibizumab and 5.9 for aflibercept (p < 0.0001). In patients continuing treatment through year 1, the number of injections was 8.0 for ranibizumab and 6.6 for aflibercept (p < 0.0001). The two cohorts had similar cause-of-discontinuation profiles. CONCLUSION: Treatment of nAMD at a single centre in two sequential cohorts yielded comparable BCVA outcomes with 15% fewer injections of aflibercept compared to ranibizumab.
Assuntos
Neovascularização de Coroide/complicações , Degeneração Macular/tratamento farmacológico , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Acuidade Visual , Idoso , Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Degeneração Macular/diagnóstico , Degeneração Macular/etiologia , Masculino , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
BACKGROUND: Congenital toxoplasmosis (CT) causes a substantial disease burden worldwide. The aim of this study was to estimate the disease burden of CT in Denmark, a developed country with free public healthcare and nationwide data available. METHODS: Using data primarily from two public health surveillance programmes conducted between 1992 and 2007, we estimated the incidence, occurrence of sequelae, mortality and the burden of disease in terms of disability-adjusted life years (DALYs) of CT in Denmark in 2014. FINDINGS: We estimated that 14 children were born with CT in 2014, of which six will have developed sequelae by the age of 12. CT resulted in a total disease burden of 123 DALYs (95% uncertainty interval [UI], 100-148), of which 78 (95% UI, 64-94) were due to foetal loss and 2 (95% UI, 1-3) were due to neonatal death; the remaining burden was due to moderate to severe life-long sequelae. A comparison of the estimated incidence of CT with the number of reported CT cases in 2008-2014 indicated that for each reported CT case, at least five other CT cases could be expected to have occurred and gone unreported. INTERPRETATION: Early onset, severity, and life-long duration of sequelae have a major effect on the disease burden of CT. Our data suggest that CT is under-diagnosed or under-reported in Denmark. The estimated disease burden and public health impact in Denmark is lower than in other European countries, highlighting the need for country-specific studies.
Assuntos
Toxoplasmose Congênita/epidemiologia , Dinamarca/epidemiologia , Humanos , IncidênciaRESUMO
PURPOSE: To assess the ocular damage that occurs in eyes with postoperative endophthalmitis after cataract surgery (PE) based on optical coherence tomography (OCT) retinal scans of PE eyes and histological specimens of eyes removed due to PE. METHODS: Case-control study and case series. Fifty-one patients who had previously developed PE were clinically examined with OCT scans of the retina of both eyes. Histological specimens of 10 removed PE eyes were studied. RESULTS: The OCT scans showed that PE eyes had a statistically significantly higher frequency of hyperdense elements on the internal limiting membrane (ILM) of the retina (14 eyes versus 3 eyes, p = 0.015) and a higher degree of retinal atrophy temporal to the fovea (13 eyes versus 1 eye, p = 0.013) compared to fellow eyes. The histopathological analyses showed the formation of epiretinal membranes, derangement of all retinal layers with a reduced number of nuclei in the nuclear layers, loss of photoreceptor outer segments and massive retinal gliosis. CONCLUSIONS: Optical coherence tomography scans of the retina and histopathology analyses provide insights in the pathological process occurring in PE.
Assuntos
Endoftalmite/patologia , Membrana Epirretiniana/patologia , Infecções Oculares Bacterianas/patologia , Degeneração Macular/patologia , Facoemulsificação , Complicações Pós-Operatórias , Retina/patologia , Atrofia , Membrana Basal/patologia , Estudos de Casos e Controles , Endoftalmite/microbiologia , Membrana Epirretiniana/microbiologia , Infecções Oculares Bacterianas/microbiologia , Feminino , Humanos , Implante de Lente Intraocular , Degeneração Macular/microbiologia , Masculino , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: There is only one prior report associating mutations in BEST1 with a diagnosis of retinitis pigmentosa (RP). The imaging studies presented in that report were more atypical of RP and shared features of autosomal recessive bestrophinopathy and autosomal dominant vitreoretinochoroidopathy. Here, we present a patient with a clinical phenotype consistent with classic features of RP. OBSERVATIONS: The patient in this report was diagnosed with simplex RP based on clinically-evident bone spicules with characteristic ERG and EOG findings. The patient had associated massive cystoid macular edema which resolved following a short course of oral acetazolamide. Genetic testing revealed that the patient carries a novel heterozygous deletion mutation in BEST1 which is not carried by either parent. While this suggests BEST1 is causative, the patient also inherited heterozygous copies of several mutations in other genes known to cause recessive retinal degenerative disease. CONCLUSIONS AND IMPORTANCE: How some mutations in BEST1 associate with peripheral retinal degeneration phenotypes, while others manifest as macular degeneration phenotypes is currently unknown. We speculate that RP due to BEST1 mutation requires mutations in other modifier genes.
RESUMO
PURPOSE: To characterize the phenotype of two families with high hypermetropia from the Faroe Islands. METHODS: Ophthalmologic evaluation including ultrasound oculometry and anthropometric measurements. RESULTS: Of the 40 examined family members, 15 individuals (8 males, 7 females; ages: 6-77 years; mean: 36.5 years) had small deep-set eyes with high hypermetropia (median: + 16.5 D; range: + 7.75 to + 22), short axial eye length (< 21 mm), and a thickened eye wall. The median corrected visual acuity was 0.4 (0.2-0.9). Ocular complications included angle-closure glaucoma in six eyes, uveal effusion in three eyes, cataract in two eyes, and esotropia with amblyopia in three eyes. An emergency case of uveal effusion and retinal detachment after Yag iridotomy eventually responded to systemic corticosteroids and scleral resection surgery with a slow visual recovery. No associated ocular or systemic malformations were found in the series. In addition to the two examined families, six smaller Faroese families with high hypermetropia are briefly reported. CONCLUSIONS: The study highlights the signs and symptoms of a rare hereditary phenotype characterized by a short axial length mainly confined to the posterior segment of the eye, a shallow anterior chamber, and a thickened eye wall. The morphological characteristics predispose for sight-threatening complications such as angle-closure glaucoma, chorioretinal pathology including uveal effusion, and amblyopia. Regular ophthalmic follow-up is therefore of obvious importance in families known to have small eyes/high hypermetropia. An endemic high prevalence in the Faroe Islands suggests the presence of a founder effect, and further genetic research would probably indicate pseudodominant rather than dominant transmission
Assuntos
Hiperopia/genética , Adolescente , Adulto , Idoso , Ambliopia/genética , Ambliopia/patologia , Ilhas Atlânticas , Catarata/genética , Catarata/patologia , Criança , Pré-Escolar , Feminino , Glaucoma de Ângulo Fechado/genética , Glaucoma de Ângulo Fechado/patologia , Humanos , Lactente , Masculino , Microftalmia/genética , Pessoa de Meia-Idade , Linhagem , Acuidade VisualRESUMO
PURPOSE: To study the relation between the interval from diagnosis to initiation of intravitreal injection therapy and visual outcome in neovascular age-related macular degeneration (nAMD) and to report changes over time in fellow-eye status. METHODS: Retrospective chart review. The study included 1185 eyes in 1099 patients who began vascular endothelial growth factor inhibitor treatment for nAMD during four separate periods in 2007, 2009, 2011 and 2012 using a fixed loading-dose regimen of three ranibizumab injections. RESULTS: Mean best-corrected visual acuity (BCVA) at presentation remained within the range 0.23-0.24 Snellen and the median patient age within 79-80 years, whereas BCVA at first visit after the third injection increased from 0.24 to 0.31 (p < 0.0001) in concert with a shift in preferred practice from separate-day injection to same-day injection. This led to a reduction in the median time to treatment from 16 days to 1 day. The proportion of patients with fellow-eye BCVA 0.05 or worse at presentation with newly diagnosed wet AMD in the incident eye decreased from 38% to 22% (p < 0.0018). The proportion of bilaterally treated patients increased during the study period. CONCLUSION: In this study, 2-week-earlier injection was associated with the equivalent of a 5-Early Treatment Diabetic Retinopathy Study letter-gain in mean visual acuity at 3 months after presentation. The difference is larger than expected from the 2-week-longer duration of disease at the study end-point. The study supports that early diagnosis and treatment of nAMD is of value for functional outcomes.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Ranibizumab/uso terapêutico , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intravítreas , Masculino , Estudos Retrospectivos , Tempo para o Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
PURPOSE: To evaluate and to compare the safety of intravitreal ranibizumab injections performed by physicians and nurses at a single large hospital clinic in Denmark during 5 years. DESIGN: Retrospective, interventional, non-comparative study. SETTING: All eyes that underwent a protocolized ranibizumab injection procedure performed in an operating room mainly by nurses and physicians in their first year of ophthalmology training. STUDY POPULATION: A total of 4623 eyes in 3679 patients with subretinal neovascularization secondary to a variety of retinal diseases, mainly neovascular AMD treated with intravitreal therapy (IVT) at the Glostrup Hospital from January 1, 2007 to December 31, 2011 with a mean follow-up of 12.2 months (95% confidence interval: 11.9-12.6). MAIN OUTCOME MEASURES: Frequency of endophthalmitis, traumatic cataract, intraocular haemorrhage and retinal detachment from 2007 to 2012. RESULTS: Overall, 38,503 intravitreal ranibizumab injections were performed in 4623 eyes. Injections were performed by nurses (32.5%), ophthalmology residents (61.3%) and vitreoretinal surgeons (6.2%). Severe complications to treatment were observed in 17 eyes: Endophthalmitis (14 eyes, 0.36 of injections whereof seven cases were culture-positive), anterior uveitis (one eye, 0.026 ), traumatic cataract (one eye, 0.026 ) and rhegmatogenous retinal detachment (one eye, 0.026 ). Retinal pigment epithelial tears were registered in 14 eyes in 14 subjects within the first year of treatment with ranibizumab. Of the 14 cases of endophthalmitis, seven occurred within a period of 5 weeks in 2010 when occasionally abnormal needle outflow resistance prompted the needle replacement in the operating room. No drug-related adverse events were recorded. CONCLUSIONS: Intravitreal ranibizumab injection performed by nurses and physicians without preinjection topical antibiotics was associated with a rate of injection-related adverse events of 0.44 .
Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Internato e Residência , Complicações Intraoperatórias , Injeções Intravítreas/efeitos adversos , Enfermeiras e Enfermeiros , Doenças Retinianas/tratamento farmacológico , Catarata/etiologia , Endoftalmite/etiologia , Hemorragia Ocular/etiologia , Humanos , Oftalmologia/educação , Ranibizumab , Descolamento Retiniano/etiologia , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome (MFS), an autosomal dominant heritable disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. FBN1 mutations have also been identified in a series of related disorders of connective tissue collectively termed type-1 fibrillinopathies. We have developed temperature-gradient gel electrophoresis (TGGE) assays for all 65 FBN1 exons, screened 126 individuals with MFS, other type-1 fibrillinopathies, and other potentially related disorders of connective tissue for FBN1 mutations, and identified a total of 53 mutations, of which 33 are described here for the first time. Several mutations were identified in individuals with fibrillinopathies other than classic Marfan syndrome, including aneurysm of the ascending aorta with only minor skeletal anomalies, and several individuals with only skeletal and ocular involvement. The mutation detection rate in this study was 42% overall, but was only 12% in individuals not fulfilling the diagnostic criteria for MFS, suggesting that clinical overdiagnosis is one reason for the low detection rate observed for FBN1 mutation analysis.
Assuntos
Eletroforese em Gel de Poliacrilamida/métodos , Éxons/genética , Síndrome de Marfan/genética , Proteínas dos Microfilamentos/genética , Adolescente , Adulto , Criança , Pré-Escolar , DNA/química , DNA/genética , Análise Mutacional de DNA , Feminino , Fibrilina-1 , Fibrilinas , Humanos , Masculino , Síndrome de Marfan/patologia , Mutação , Reação em Cadeia da PolimeraseRESUMO
PURPOSE: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age-related macular degeneration (AMD). METHODS: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria and were treated with repeated intravitreal injections of ranibizumab 0.5 mg in routine clinical practice, beginning with three initial injections at 4-week intervals followed by individualized retreatment for the subsequent 9 months. Study parameters included best-corrected visual acuity (BCVA) and morphological characteristics. RESULTS: Mean BCVA relative to baseline was +4.7 (p < 0.0001), +4.2 (p < 0.0001)and -0.4 (p > 0.667) Early Treatment Diabetic Retinopathy Study letters after 3, 6 and 12 months, respectively, after a mean of 5.1 injections when the proportion of patients with BCVA ≥ 70 letters had doubled compared with baseline. Predictive factors for BCVA ≤ 35 letters after 12 months were BCVA ≤ 35 letters at baseline and month 3 (p < 0.0001) while BCVA ≥ 70 letters at month 12 was associated with BCVA ≥ 70 letters at baseline and month 3 (p < 0.001) and with total lesion size <4 DA (p = 0.0147). CONCLUSION: Under a ranibizumab regimen with substantially fewer injections than with fixed four-weekly injection regimens, BCVA was improved compared with the natural history of neovascular AMD, but did not achieve the visual gain observed in randomized clinical trials using fixed 4-week retreatment. Visual acuity at month 3, after the initial fixed-interval injections, was the strongest predictor of BCVA at month 12.