Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review. OBJECTIVES: To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers, most recently on 29 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation to placebo or no intervention, in people with AMD. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. MAIN RESULTS: We included 26 studies conducted in the USA, Europe, China, and Australia. These studies enroled 11,952 people aged 65 to 75 years and included slightly more women (on average 56% women). We judged the studies that contributed data to the review to be at low or unclear risk of bias. Thirteen studies compared multivitamins with control in people with early and intermediate AMD. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, 2445 participants; moderate-certainty evidence). In people with early AMD, who are at low risk of progression, this means there would be approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). In people with intermediate AMD at higher risk of progression, this corresponds to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer). AREDS also provided evidence of a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence), and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (measured with the Visual Function Questionnaire) in treated compared with non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). In exploratory subgroup analyses in the follow-on study to AREDS (AREDS2), replacing beta-carotene with lutein/zeaxanthin gave hazard ratios (HR) of 0.82 (95% CI 0.69 to 0.96), 0.78 (95% CI 0.64 to 0.94), 0.94 (95% CI 0.70 to 1.26), and 0.88 (95% CI 0.75 to 1.03) for progression to late AMD, neovascular AMD, geographic atrophy, and vision loss, respectively. Six studies compared lutein (with or without zeaxanthin) with placebo and one study compared a multivitamin including lutein/zeaxanthin with multivitamin alone. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA; almost all participants in AREDS2 also took the original AREDS supplementation formula. People taking lutein/zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05) compared with control (1 study, 4176 participants, 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein/zeaxanthin and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (Visual Function Questionnaire) was similar between groups (MD 1.21, 95% CI -2.59 to 5.01; 2 studies, 308 participants; moderate-certainty evidence). One study in Australia randomised 1204 people to vitamin E or placebo with four years of follow-up; 19% of participants had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05; very low-certainty evidence). There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47; low-certainty evidence). There were no data on neovascular AMD, geographic atrophy, or quality of life. Five studies compared zinc with placebo. Evidence largely drawn from the largest study (AREDS) found a lower progression to late AMD over six years (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, 3790 participants; moderate-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 2 studies, 3791 participants; moderate-certainty evidence). There were no data on quality of life. Gastrointestinal symptoms were the main reported adverse effect. In AREDS, zinc was associated with a higher risk of genitourinary problems in men, but no difference was seen between high- and low-dose zinc groups in AREDS2. Most studies were too small to detect rare adverse effects. Data from larger studies (AREDS/AREDS2) suggested there may be little or no effect on mortality with multivitamin (HR 0.87, 95% CI 0.60 to 1.25; low-certainty evidence) or lutein/zeaxanthin supplementation (HR 1.06, 95% CI 0.87 to 1.31; very low-certainty evidence), but confirmed the increased risk of lung cancer with beta-carotene, mostly in former smokers. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.

Artificial intelligence for diabetic retinopathy in low-income and middle-income countries: a scoping review.

Diabetic retinopathy (DR) is a leading cause of blindness globally. There is growing evidence to support the use of artificial intelligence (AI) in diabetic eye care, particularly for screening populations at risk of sight loss from DR in low-income and middle-income countries (LMICs) where resources are most stretched. However, implementation into clinical practice remains limited. We conducted a scoping review to identify what AI tools have been used for DR in LMICs and to report their performance and relevant characteristics. 81 articles were included. The reported sensitivities and specificities were generally high providing evidence to support use in clinical practice. However, the majority of studies focused on sensitivity and specificity only and there was limited information on cost, regulatory approvals and whether the use of AI improved health outcomes. Further research that goes beyond reporting sensitivities and specificities is needed prior to wider implementation.

Laser-assisted cataract surgery versus standard ultrasound phacoemulsification cataract surgery.

BACKGROUND: Cataract is the leading cause of blindness in the world and, as such, cataract surgery is one of the most commonly performed operations globally. Surgical techniques have changed dramatically over the past half century with associated improvements in outcomes and safety. Femtosecond lasers can be used to perform the key steps in cataract surgery, such as corneal incisions, lens capsulotomy and fragmentation. The potential advantage of femtosecond laser-assisted cataract surgery (FLACS) is greater precision and reproducibility of these steps compared to manual techniques. The disadvantages are the costs associated with FLACS technology. OBJECTIVES: To compare the effectiveness and safety of FLACS with standard ultrasound phacoemulsification cataract surgery (PCS) by gathering evidence from randomised controlled trials (RCTs). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov; the WHO ICTRP and the US Food and Drug Administration (FDA) website. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 May 2022. SELECTION CRITERIA: We included RCTs where FLACS was compared to PCS. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the search results, assessed risk of bias and extracted data using the standard methodological procedures expected by Cochrane. The primary outcome for this review was intraoperative complications in the operated eye, namely anterior capsule, and posterior capsule tears. The secondary outcomes included corrected distance visual acuity (CDVA), quality of vision (as measured by any validated patient-reported outcome measure (PROM)), postoperative cystoid macular oedema complications, endothelial cell loss and cost-effectiveness. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 42 RCTs conducted in Europe, North America, South America and Asia, which enrolled a total of 7298 eyes of 5831 adult participants. Overall, the studies were at unclear or high risk of bias. In 16 studies the authors reported financial links with the manufacturer of the laser platform evaluated in their studies. Thirteen of the studies were within-person (paired-eye) studies with one eye allocated to one procedure and the other eye allocated to the other procedure. These studies were reported ignoring the paired nature of the data. There was low-certainty evidence of little or no difference in the odds of developing anterior capsular tears when comparing FLACS and PCS (Peto odds ratio (OR) 0.83, 95% confidence interval (CI) 0.40 to 1.72; 5835 eyes, 27 studies) There was one fewer anterior capsule tear per 1000 operations in the FLACS group compared with the PCS group (95% CI 4 fewer to 3 more).  There was low-certainty evidence of lower odds of developing posterior capsular tears with FLACS compared to PCS (Peto OR 0.50, 95% CI 0.25 to 1.00; 5767 eyes, 26 studies). There were four fewer posterior capsule tears per 1000 operations in the FLACS group compared with the PCS group (95% CI 6 fewer to same).  There was moderate-certainty evidence of a very small advantage for the FLACS arm with regard to CDVA at six months or more follow-up, (mean difference (MD) -0.01 logMAR, 95% CI -0.02 to 0.00; 1323 eyes, 7 studies). This difference is equivalent to 1 logMAR letter between groups and is not thought to be clinically important. From the three studies (1205 participants) reporting a variety of PROMs (Cat-PROMS, EQ-5D, EQ-SD-3L, Catquest9-SF and patient survey) up to three months following surgery, there was moderate-certainty evidence of little or no difference in the various parameters between the two treatment arms. There was low-certainty evidence of little or no difference in the odds of developing cystoid macular oedema when comparing FLACS and PCS (Peto OR 0.84, 95% CI 0.56 to 1.28; 4441 eyes, 18 studies). There were three fewer cystoid macular oedema cases per 1000 operations in the FLACS group compared with the PCS group (95% CI 10 fewer to 6 more).  In one study the incremental cost-effectiveness ratio (ICER) (cost difference divided by quality-adjusted life year (QALY) difference) was GBP £167,620 when comparing FLACS to PCS. In another study, the ICER was EUR €10,703 saved per additional patient who had treatment success with PCS compared to FLACS. Duration ranged from three minutes in favour of FLACS to eight minutes in favour of PCS (I2 = 100%, 11 studies) (low-certainty evidence).  There was low-certainty evidence of little or no important difference in endothelial cell loss when comparing FLACS with PCS (MD 12 cells per mm2 in favour of FLACS, 95% CI -40 to 64; 1512 eyes, 10 studies).  AUTHORS' CONCLUSIONS: This review of 42 studies provides evidence that there is probably little or no difference between FLACS and PCS in terms of intraoperative and postoperative complications, postoperative visual acuity and quality of life. Evidence from two studies suggests that FLACS may be the less cost-effective option. Many of the included studies only investigated very specific outcome measures such as effective phacoemulsification time, endothelial cell count change or aqueous flare, rather than those directly related to patient outcomes. Standardised reporting of complications and visual and refractive outcomes for cataract surgery would facilitate future synthesis, and guidance on this has been recently published.

ANTECEDENTES: La catarata es la principal causa de ceguera en el mundo y, como tal, la cirugía de cataratas es una de las operaciones más realizadas en todo el mundo. Las técnicas quirúrgicas han cambiado radicalmente en el último medio siglo, con las consiguientes mejoras en los desenlaces y la seguridad. Los láseres de femtosegundo se pueden utilizar para realizar los pasos clave de la cirugía de cataratas, como las incisiones corneales, la capsulotomía y la fragmentación del cristalino. La ventaja potencial de la cirugía de cataratas asistida por láser de femtosegundo (FLACS por sus siglas en inglés) es la mayor precisión y reproducibilidad de estos pasos en comparación con las técnicas manuales. Las desventajas son los costes asociados con la tecnología FLACS. OBJETIVOS: Comparar la eficacia y la seguridad de la FLACS con la cirugía de cataratas estándar por facoemulsificación (PCS) con ultrasonido mediante la recopilación de evidencia de ensayos controlados aleatorizados (ECA). MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en el Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials [CENTRAL]; que contiene el Registro de ensayos del Grupo Cochrane de Salud ocular y de la visión [Cochrane Eyes and Vision]; 2022, número 5); en Ovid MEDLINE; Ovid Embase; LILACS; el registro ISRCTN; ClinicalTrials.gov; la ICTRP de la OMS y el sitio web de la Food and Drug Administration (FDA) de los EE. UU. No se aplicaron restricciones de fecha ni de idioma en las búsquedas electrónicas de ensayos. La última búsqueda en las bases de datos electrónicas se realizó el 10 de mayo de 2022. CRITERIOS DE SELECCIÓN: Se incluyeron los ECA en los que la FLACS se comparó con la PCS. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Tres autores de la revisión examinaron de forma independiente los resultados de la búsqueda, evaluaron el riesgo de sesgo y extrajeron los datos mediante los procedimientos metodológicos estándar previstos por Cochrane. El desenlace principal de esta revisión fueron las complicaciones intraoperatorias en el ojo operado, concretamente, desgarros de la cápsula anterior y posterior. Los desenlaces secundarios incluyeron la agudeza visual corregida a distancia (AVCD), la calidad de la visión (medida por cualquier medida de desenlace notificada por el paciente [PROM] validada), las complicaciones posoperatorias del edema macular cistoide, la pérdida de células endoteliales y la coste­efectividad. La certeza de la evidencia se evaluó mediante el método GRADE. RESULTADOS PRINCIPALES: Se incluyeron 42 ECA realizados en Europa, Norteamérica, Sudamérica y Asia, que reclutaron un total de 7298 ojos de 5831 participantes adultos. En general, los estudios tuvieron riesgo de sesgo incierto o alto. En 16 estudios, los autores informaron vínculos financieros con el fabricante de la plataforma láser evaluada en sus estudios. Trece de los estudios fueron estudios intrapersonales (ojo pareado) con un ojo asignado a un procedimiento y el otro ojo asignado al otro procedimiento. El informe de estos estudios no consideró la naturaleza pareada de los datos. Hubo evidencia de certeza baja de poca o ninguna diferencia en las probabilidades de desarrollar desgarros de la cápsula anterior al comparar FLACS y PCS (odds ratio [OR] de Peto 0,83; intervalo de confianza [IC] del 95%: 0,40 a 1,72; 5835 ojos, 27 estudios). Hubo un desgarro de la cápsula anterior menos por cada 1000 cirugías en el grupo de FLACS en comparación con el grupo de PCS (IC del 95%: 4 menos a 3 más).  Hubo evidencia de certeza baja de menores probabilidades de desarrollar desgarros de la cápsula posterior con FLACS en comparación con PCS (OR de Peto 0,50; IC del 95%: 0,25 a 1,00; 5767 ojos, 26 estudios). Hubo cuatro desgarros de la cápsula posterior menos por cada 1000 cirugías en el grupo de FLACS en comparación con el grupo de PCS (IC del 95%: 6 menos a igual).  Hubo evidencia de certeza moderada de una ventaja muy pequeña en el grupo de FLACS con respecto a la AVCD a los seis meses o más de seguimiento, (diferencia de medias [DM] ­0,01 logMAR; IC del 95%: ­0,02 a 0,00; 1323 ojos, siete estudios). Esta diferencia equivale a 1 letra logMAR entre los grupos y no se considera clínicamente importante. De los tres estudios (1205 participantes) que informaron sobre una variedad de PROM (Cat­PROMS, EQ­5D, EQ­SD­3L, Catquest9­SF y encuesta de pacientes) hasta tres meses después de la cirugía, hubo evidencia de certeza moderada de poca o ninguna diferencia en los diversos parámetros entre los dos grupos de tratamiento. Hubo evidencia de certeza baja de poca o ninguna diferencia en las probabilidades de desarrollar edema macular cistoide al comparar FLACS y PCS (OR de Peto 0,84; IC del 95%: 0,56 a 1,28; 4441 ojos, 18 estudios). Hubo tres casos menos de edema macular cistoide por cada 1000 cirugías en el grupo de FLACS en comparación con el grupo de PCS (IC del 95%: 10 menos a 6 más).  En un estudio, el cociente coste­efectividad incremental (ICER) (diferencia de coste dividida por la diferencia de años de vida ajustados por la calidad [AVAC]) fue de 167 620 GBP al comparar FLACS con SCP. En otro estudio, el ICER fue de 10 703 euros ahorrados por paciente adicional que tuvo un tratamiento exitoso con PCS en comparación con FLACS. La duración varió entre tres minutos a favor de FLACS y ocho minutos a favor de PCS (I 2 = 100%, 11 estudios) (evidencia de certeza baja).  Hubo evidencia de certeza baja de poca o ninguna diferencia importante en la pérdida de células endoteliales al comparar la FLACS con la PCS (DM 12 células por mm 2 a favor de la FLACS; IC del 95%: ­40 a 64; 1512 ojos, 10 estudios).  CONCLUSIONES DE LOS AUTORES: Esta revisión de 42 estudios aporta evidencia de que probablemente haya poca o ninguna diferencia entre la FLACS y la PCS en cuanto a las complicaciones intraoperatorias y posoperatorias, la agudeza visual posoperatoria y la calidad de vida. La evidencia de dos estudios indica que la FLACS podría ser la opción menos coste­efectiva. Muchos de los estudios incluidos solo investigaron medidas de desenlace muy específicas, como el tiempo efectivo de facoemulsificación, el cambio en el recuento de células endoteliales o el brote acuoso, en lugar de las directamente relacionadas con los desenlaces de los pacientes. La notificación estandarizada de las complicaciones y los desenlaces visuales y refractarios de la cirugía de cataratas facilitaría la síntesis futura, y recientemente se han publicado guías al respecto.

Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most serious complication of DR and can lead to total (central and peripheral) visual loss. PDR is characterised by the presence of abnormal new blood vessels, so-called "new vessels," at the optic disc (NVD) or elsewhere in the retina (NVE). PDR can progress to high-risk characteristics (HRC) PDR (HRC-PDR), which is defined by the presence of NVD more than one-fourth to one-third disc area in size plus vitreous haemorrhage or pre-retinal haemorrhage, or vitreous haemorrhage or pre-retinal haemorrhage obscuring more than one disc area. In severe cases, fibrovascular membranes grow over the retinal surface and tractional retinal detachment with sight loss can occur, despite treatment. Although most, if not all, individuals with diabetes will develop DR if they live long enough, only some progress to the sight-threatening PDR stage.  OBJECTIVES: To determine risk factors for the development of PDR and HRC-PDR in people with diabetes and DR. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5), Ovid MEDLINE, and Ovid Embase. The date of the search was 27 May 2022. Additionally, the search was supplemented by screening reference lists of eligible articles. There were no restrictions to language or year of publication.  SELECTION CRITERIA: We included prospective or retrospective cohort studies and case-control longitudinal studies evaluating prognostic factors for the development and progression of PDR, in people who have not had previous treatment for DR. The target population consisted of adults (≥18 years of age) of any gender, sexual orientation, ethnicity, socioeconomic status, and geographical location, with non-proliferative diabetic retinopathy (NPDR) or PDR with less than HRC-PDR, diagnosed as per standard clinical practice. Two review authors independently screened titles and abstracts, and full-text articles, to determine eligibility; discrepancies were resolved through discussion. We considered prognostic factors measured at baseline and any other time points during the study and in any clinical setting. Outcomes were evaluated at three and eight years (± two years) or lifelong.  DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included studies using a data extraction form that we developed and piloted prior to the data collection stage. We resolved any discrepancies through discussion. We used the Quality in Prognosis Studies (QUIPS) tool to assess risk of bias. We conducted meta-analyses in clinically relevant groups using a random-effects approach. We reported hazard ratios (HR), odds ratios (OR), and risk ratios (RR) separately for each available prognostic factor and outcome, stratified by different time points. Where possible, we meta-analysed adjusted prognostic factors. We evaluated the certainty of the evidence with an adapted version of the GRADE framework.   MAIN RESULTS: We screened 6391 records. From these, we identified 59 studies (87 articles) as eligible for inclusion. Thirty-five were prospective cohort studies, 22 were retrospective studies, 18 of which were cohort and six were based on data from electronic registers, and two were retrospective case-control studies. Twenty-three studies evaluated participants with type 1 diabetes (T1D), 19 with type 2 diabetes (T2D), and 17 included mixed populations (T1D and T2D). Studies on T1D included between 39 and 3250 participants at baseline, followed up for one to 45 years. Studies on T2D included between 100 and 71,817 participants at baseline, followed up for one to 20 years. The studies on mixed populations of T1D and T2D ranged from 76 to 32,553 participants at baseline, followed up for four to 25 years.  We found evidence indicating that higher glycated haemoglobin (haemoglobin A1c (HbA1c)) levels (adjusted OR ranged from 1.11 (95% confidence interval (CI) 0.93 to 1.32) to 2.10 (95% CI 1.64 to 2.69) and more advanced stages of retinopathy (adjusted OR ranged from 1.38 (95% CI 1.29 to 1.48) to 12.40 (95% CI 5.31 to 28.98) are independent risk factors for the development of PDR in people with T1D and T2D. We rated the evidence for these factors as of moderate certainty because of moderate to high risk of bias in the studies.  There was also some evidence suggesting several markers for renal disease (for example, nephropathy (adjusted OR ranged from 1.58 (95% CI not reported) to 2.68 (2.09 to 3.42), and creatinine (adjusted meta-analysis HR 1.61 (95% CI 0.77 to 3.36)), and, in people with T1D, age at diagnosis of diabetes (< 12 years of age) (standardised regression estimate 1.62, 95% CI 1.06 to 2.48), increased triglyceride levels (adjusted RR 1.55, 95% CI 1.06 to 1.95), and larger retinal venular diameters (RR 4.28, 95% CI 1.50 to 12.19) may increase the risk of progression to PDR. The certainty of evidence for these factors, however, was low to very low, due to risk of bias in the included studies, inconsistency (lack of studies preventing the grading of consistency or variable outcomes), and imprecision (wide CIs). There was no substantial and consistent evidence to support duration of diabetes, systolic or diastolic blood pressure, total cholesterol, low- (LDL) and high- (HDL) density lipoproteins, gender, ethnicity, body mass index (BMI), socioeconomic status, or tobacco and alcohol consumption as being associated with incidence of PDR. There was insufficient evidence to evaluate prognostic factors associated with progression of PDR to HRC-PDR.  AUTHORS' CONCLUSIONS: Increased HbA1c is likely to be associated with progression to PDR; therefore, maintaining adequate glucose control throughout life, irrespective of stage of DR severity, may help to prevent progression to PDR and risk of its sight-threatening complications. Renal impairment in people with T1D or T2D, as well as younger age at diagnosis of diabetes mellitus (DM), increased triglyceride levels, and increased retinal venular diameters in people with T1D may also be associated with increased risk of progression to PDR. Given that more advanced DR severity is associated with higher risk of progression to PDR, the earlier the disease is identified, and the above systemic risk factors are controlled, the greater the chance of reducing the risk of PDR and saving sight.

ANTECEDENTES: La retinopatía diabética (RD) se caracteriza por la degeneración neurovascular como consecuencia de la hiperglucemia crónica. La retinopatía diabética proliferativa (RDP) es la complicación más grave de la RD y puede provocar una pérdida total (central y periférica) de la visión. La RDP se caracteriza por la presencia de vasos sanguíneos de neoformación anormales, neovascularización, en la papila óptica (NVP) o en cualquier otra parte de la retina (NVE). La RDP puede evolucionar a una RDP con características de alto riesgo (RDP­CAR), que se define por la presencia de NVP de más de un cuarto a un tercio del área discal más hemorragia vítrea o prerretiniana, o hemorragia vítrea o prerretiniana que oscurece más de un área papilar. En los casos graves, crecen membranas fibrovasculares sobre la superficie retiniana y se puede producir un desprendimiento de retina por tracción con pérdida de la visión, a pesar del tratamiento. Aunque la mayoría de las personas con diabetes, si no todas, desarrollarán RD si viven lo suficiente, solo algunas llegan a la fase de RDP, que pone en peligro la vista. OBJETIVOS: Determinar los factores de riesgo de aparición de la RDP y RDP­CAR en personas con diabetes y RD. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en el Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials, CENTRAL; que contiene el Registro de ensayos del Grupo Cochrane de Salud ocular y de la visión [Cochrane Eyes and Vision]; 2022, número 5), Ovid MEDLINE y Ovid Embase. La fecha de búsqueda fue el 27 de mayo de 2022. Además, la búsqueda se complementó con el cribado de las listas de referencias de los artículos elegibles. No hubo restricciones en cuanto al idioma ni al año de publicación. CRITERIOS DE SELECCIÓN: Se incluyeron estudios de cohortes prospectivos o retrospectivos y estudios longitudinales de casos y controles que evaluaran los factores pronósticos para la aparición y la progresión de la RDP, en personas que no habían recibido tratamiento previo para la RD. La población de interés estaba formada por adultos (≥18 años de edad) de cualquier sexo, orientación sexual, etnia, nivel socioeconómico y ubicación geográfica, con retinopatía diabética no proliferativa (RDNP) o RDP sin llegar a RDP­CAR, diagnosticada según la práctica clínica habitual. Dos autores de la revisión examinaron de forma independiente los títulos y resúmenes, así como los artículos completos, para determinar la elegibilidad; las discrepancias se resolvieron mediante debate. Se tuvieron en cuenta los factores pronósticos medidos al inicio del estudio y en cualquier otro punto temporal durante el estudio y en cualquier contexto clínico. Los desenlaces se evaluaron a los tres y ocho años (± dos años) o de por vida. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión extrajeron de forma independiente los datos de los estudios incluidos mediante un formulario de extracción de datos que se desarrolló y evaluó antes de la etapa de obtención de datos. Las discrepancias se resolvieron mediante debate. Para evaluar el riesgo de sesgo se utilizó la herramienta Quality in Prognosis Studies (QUIPS). Se realizaron metanálisis en grupos clínicamente relevantes utilizando un enfoque de efectos aleatorios. Se proporcionaron los cociente de riesgos instantáneos (CRI), los odds ratios (OR) y las razones de riesgos (RR) por separado para cada factor pronóstico y desenlace disponibles, estratificados por diferentes puntos temporales. Cuando fue posible, se realizó un metanálisis de los factores pronósticos ajustados. La certeza de la evidencia se evaluó con una versión adaptada del método GRADE. RESULTADOS PRINCIPALES: Se han examinado 6391 registros. A partir de estos se identificaron 59 estudios (87 artículos) elegibles para inclusión. Treinta y cinco fueron estudios de cohortes prospectivos, 22 fueron estudios retrospectivos, 18 de los cuales fueron de cohortes y 6 se basaron en datos de registros electrónicos, y 2 fueron estudios retrospectivos de casos y controles. Veintitrés estudios evaluaron a participantes con diabetes tipo 1 (DT1), 19 con diabetes tipo 2 (DT2) y 17 incluyeron poblaciones mixtas (DT1 y DT2). Los estudios sobre la DT1 incluyeron entre 39 y 3250 participantes al inicio del estudio, con un seguimiento de 1 a 45 años. Los estudios sobre la DT2 incluyeron entre 100 y 71 817 participantes al inicio del estudio, con un seguimiento de 1 a 20 años. Los estudios sobre poblaciones mixtas de DT1 y DT2 variaron entre 76 y 32 553 participantes al inicio del estudio, con un seguimiento de 4 a 25 años. Se encontró evidencia que indicó que los niveles más altos de hemoglobina glucosilada (hemoglobina A1c [HbA1c]) (OR ajustado que varió de 1,11 [intervalo de confianza (IC) del 95%: 0,93 a 1,32] a 2,10 [IC del 95%: 1,64 a 2,69]) y los estadios más avanzados de retinopatía (OR ajustado que varió entre 1,38 [IC del 95%: 1,29 a 1,48] y 12,40 [IC del 95%: 5,31 a 28,98]) son factores de riesgo independientes para el desarrollo de RDP en personas con DT1 y DT2. La evidencia para estos factores se consideró de certeza moderada debido al riesgo moderado a alto de sesgo en los estudios. También hubo alguna evidencia que indicó varios marcadores de enfermedad renal (por ejemplo, nefropatía [OR ajustado que varió entre 1,58 (IC del 95% no proporcionado) y 2,68 (2,09 a 3,42)] y creatinina [metanálisis ajustado CRI 1,61 (IC del 95%: 0,77 a 3.36)]), y, en las personas con DT1, la edad en el momento del diagnóstico de la diabetes (< 12 años) (estimación de la regresión estandarizada 1,62; IC del 95%: 1,06 a 2,48), el aumento de los niveles de triglicéridos (RR ajustado 1,55; IC del 95%: 1,06 a 1,95) y los diámetros venulares retinianos mayores (RR 4,28; IC del 95%: 1,50 a 12,19) podrían aumentar el riesgo de progresión a RDP. Sin embargo, la certeza de la evidencia para estos factores fue de baja a muy baja, debido al riesgo de sesgo en los estudios incluidos, la inconsistencia (falta de estudios que impide la calificación de consistencia o desenlaces variables) y la imprecisión (IC amplios). No hubo evidencia importante ni consistente que apoyara que la duración de la diabetes, la presión arterial sistólica o diastólica, el colesterol total, las lipoproteínas de baja (LDL) y alta (HDL) densidad, el sexo, el origen étnico, el índice de masa corporal (IMC), el nivel socioeconómico o el consumo de tabaco y alcohol estuvieran asociados con la incidencia de RDP. No hubo evidencia suficiente para evaluar los factores pronósticos asociados con la progresión de la RDP a RDP­CAR. CONCLUSIONES DE LOS AUTORES: Es probable que el aumento de la HbA1c se asocie con la progresión a la RDP; por lo tanto, mantener un control adecuado de la glucosa durante toda la vida, independientemente del estadio de gravedad de la RD, podría ayudar a prevenir la progresión a la RDP y el riesgo de sus complicaciones que ponen en peligro la vista. La insuficiencia renal en personas con DT1 o DT2, así como una menor edad en el momento del diagnóstico de la diabetes mellitus (DM), el aumento de los niveles de triglicéridos y el aumento de los diámetros venulares retinianos en personas con DT1 también se podrían asociar con un mayor riesgo de progresión a RDP. Dado que la gravedad más avanzada de la RD se asocia con un mayor riesgo de progresión a RDP, cuanto antes se identifique la enfermedad y se controlen los factores de riesgo sistémicos mencionados, mayores serán las posibilidades de reducir el riesgo de RDP y conservar la vista.

Effective cataract surgical coverage in adults aged 50 years and older: estimates from population-based surveys in 55 countries.

BACKGROUND: Cataract is the leading cause of blindness globally. Effective cataract surgical coverage (eCSC) measures the number of people in a population who have been operated on for cataract, and had a good outcome, as a proportion of all people operated on or requiring surgery. Therefore, eCSC describes service access (ie, cataract surgical coverage, [CSC]) adjusted for quality. The 74th World Health Assembly endorsed a global target for eCSC of a 30-percentage point increase by 2030. To enable monitoring of progress towards this target, we analysed Rapid Assessment of Avoidable Blindness (RAAB) survey data to establish baseline estimates of eCSC and CSC. METHODS: In this secondary analysis, we used data from 148 RAAB surveys undertaken in 55 countries (2003-21) to calculate eCSC, CSC, and the relative quality gap (% difference between eCSC and CSC). Eligible studies were any version of the RAAB survey conducted since 2000 with individual participant survey data and census population data for people aged 50 years or older in the sampling area and permission from the study's principal investigator for use of data. We compared median eCSC between WHO regions and World Bank income strata and calculated the pooled risk difference and risk ratio comparing eCSC in men and women. FINDINGS: Country eCSC estimates ranged from 3·8% (95% CI 2·1-5·5) in Guinea Bissau, 2010, to 70·3% (95% CI 65·8-74·9) in Hungary, 2015, and the relative quality gap from 10·8% (CSC: 65·7%, eCSC: 58·6%) in Argentina, 2013, to 73·4% (CSC: 14·3%, eCSC: 3·8%) in Guinea Bissau, 2010. Median eCSC was highest among high-income countries (60·5% [IQR 55·6-65·4]; n=2 surveys; 2011-15) and lowest among low-income countries (14·8%; [IQR 8·3-20·7]; n=14 surveys; 2005-21). eCSC was higher in men than women (148 studies pooled risk difference 3·2% [95% CI 2·3-4·1] and pooled risk ratio of 1·20 [95% CI 1·15-1·25]). INTERPRETATION: eCSC varies widely between countries, increases with greater income level, and is higher in men. In pursuit of 2030 targets, many countries, particularly in lower-resource settings, should emphasise quality improvement before increasing access to surgery. Equity must be embedded in efforts to improve access to surgery, with a focus on underserved groups. FUNDING: Indigo Trust, Peek Vision, and Wellcome Trust.

Universal newborn eye screening: a systematic review of the literature and review of international guidelines.

Background: This systematic review assessed the effectiveness of universal screening for newborn eye abnormalities compared with no screening in improving infant vision and health outcomes. Methods: We searched CENTRAL (Cochrane Library), MEDLINE, Embase, Global Health, Global Index Medicus, clinical trials databases, and bibliographies of relevant articles. We included randomized and observational studies of all newborns, regardless of illness or risk factors, that compared universal screening for any eye abnormality by eight weeks of age with no universal screening. Two authors independently selected studies, extracted data, and evaluated the risk of bias. We used GRADE to assess the certainty of evidence. We also reviewed available recommendations on newborn eye screening. Results: Fourteen studies were identified but only three compared universal red reflex screening with no screening. Findings suggest that universal red reflex testing in maternity wards (MWs) may increase the number of newborns with congenital cataracts referred for eye care from MWs or well-baby clinics (WBCs) in the first year of life (risk ratio (RR) = 9.83, 95% confidence interval (CI) = 1.36-71.20; low certainty evidence). However, the effect of screening in WBC is uncertain (RR = 6.62, 95% CI = 0.87-50.09). The effect of MW or WBC screening on referral from any health care facility (MWs, WBCs, paediatrician clinic, other) in the first year is uncertain (MW screening: RR = 1.22, 95% CI = 0.63-2.39; WBC screening: RR = 0.97, 95% CI = 0.46-2.05). However, referral or surgery by 6 weeks of age may be higher with universal MW screening (early referral: RR = 4.61, 95% CI = 1.12-19.01; early surgery: RR = 8.23, 95% CI = 1.13-59.80; low certainty evidence). The effect of WBC screening on early referral and surgery is uncertain (early referral: RR = 1.98, 95% CI = 0.43-9.19; early surgery: RR = 3.97, 95% CI = 0.50-31.33; very low certainty evidence). Universal red reflex testing may increase clinical conjunctivitis (OR = 1.22, 95% CI = 1.01-1.47; low certainty evidence) but the effect on confirmed bacterial conjunctivitis is uncertain (OR = 1.20, 95% CI = 0.76-1.90; very low-certainty evidence). Nine guidelines recommended universal newborn eye screening using red reflex testing. Conclusions: Evidence supports the role of red reflex testing shortly after birth to increase early identification, referral, and surgery for congenital cataracts.

Laser trabeculoplasty for open-angle glaucoma and ocular hypertension.

BACKGROUND: Open-angle glaucoma (OAG) is an important cause of blindness worldwide. Laser trabeculoplasty, a treatment modality, still does not have a clear position in the treatment sequence. OBJECTIVES: To assess the effects of laser trabeculoplasty for treating OAG and ocular hypertension (OHT) when compared to medication, glaucoma surgery or no intervention. We also wished to compare the effectiveness of different laser trabeculoplasty technologies for treating OAG and OHT. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; LILACS, ClinicalTrials.gov and the WHO ICTRP. The date of the search was 28 October 2021. We also contacted researchers in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing laser trabeculoplasty with no intervention, with medical treatment, or with surgery in people with OAG or OHT. We also included trials comparing different types of laser trabeculoplasty technologies. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Two authors screened search results and extracted data independently. We considered the following outcomes at 24 months: failure to control intraocular pressure (IOP), failure to stabilise visual field progression, failure to stabilise optic neuropathy progression, adverse effects, quality of life, and costs. We graded the 'certainty' of the evidence using GRADE. MAIN RESULTS: We included 40 studies (5613 eyes of 4028 people) in this review. The majority of the studies were conducted in Europe and in the USA. Most of the studies were at risk of performance and/or detection bias as they were unmasked. None of the studies were judged as having low risk of bias for all domains. We did not identify any studies of laser trabeculoplasty alone versus no intervention. Laser trabeculoplasty versus medication Fourteen studies compared laser trabeculoplasty with medication in either people with primary OAG (7 studies) or primary or secondary OAG (7 studies); five of the 14 studies also included participants with OHT. Six studies used argon laser trabeculoplasty and eight studies used selective laser trabeculoplasty. There was considerable clinical and methodological diversity in these studies leading to statistical heterogeneity in results for the primary outcome "failure to control IOP" at 24 months.  Risk ratios (RRs) ranged from 0.43 in favour of laser trabeculoplasty to 1.87 in favour of medication (5 studies, I2 = 89%). Studies of argon laser compared with medication were more likely to show a beneficial effect compared with studies of selective laser (test for interaction P = 0.0001) but the argon laser studies were older and the medication comparator group in those studies may have been less effective. We considered this to be low-certainty evidence because the trials were at risk of bias (they were not masked) and there was unexplained heterogeneity. There was evidence from two studies (624 eyes) that argon laser treatment was associated with less failure to stabilise visual field progression compared with medication (7% versus 11%, RR 0.70, 95% CI 0.42 to 1.16) at 24 months and one further large recent study of selective laser also reported a reduced risk of failure at 48 months (17% versus 26%) RR 0.65, 95% CI 0.52 to 0.81, 1178 eyes). We judged this outcome as moderate-certainty evidence, downgrading for risk of bias. There was only very low-certainty evidence on optic neuropathy progression. Adverse effects were more commonly seen in the laser trabeculoplasty group including peripheral anterior synechiae (PAS) associated with argon laser (32% versus 26%, RR 11.74, 95% CI 5.94 to 23.22; 624 eyes; 2 RCTs; low-certainty evidence); 5% of participants treated with laser in three studies of selective laser group had early IOP spikes (moderate-certainty evidence). One UK-based study provided moderate-certainty evidence that laser trabeculoplasty was more cost-effective.  Laser trabeculoplasty versus trabeculectomy Three studies compared laser trabeculoplasty with trabeculectomy. All three studies enrolled participants with OAG (primary or secondary) and used argon laser. People receiving laser trabeculoplasty may have a higher risk of uncontrolled IOP at 24 months compared with people receiving trabeculectomy (16% versus 8%, RR 2.12, 95% CI 1.44 to 3.11; 901 eyes; 2 RCTs). We judged this to be low-certainty evidence because of risk of bias (trials were not masked) and there was inconsistency between the two trials (I2 = 68%). There was limited evidence on visual field progression suggesting a higher risk of failure with laser trabeculoplasty. There was no information on optic neuropathy progression, quality of life or costs. PAS formation and IOP spikes were not reported but in one study trabeculectomy was associated with an increased risk of cataract (RR 1.78, 95% CI 1.46 to 2.16) (very low-certainty evidence). AUTHORS' CONCLUSIONS: Laser trabeculoplasty may work better than topical medication in slowing down the progression of open-angle glaucoma (rate of visual field loss) and may be similar to modern eye drops in controlling eye pressure at a lower cost. It is not associated with serious unwanted effects, particularly for the newer types of trabeculoplasty, such as selective laser trabeculoplasty.

A systematic review of clinical practice guidelines for childhood glaucoma.

OBJECTIVE: To conduct a systematic review to identify and critically appraise clinical practice guidelines on the assessment, diagnosis and management of childhood glaucoma. METHODS AND ANALYSIS: A systematic literature search of databases and professional websites for clinical practice guidelines published on eye conditions between 2010 and April 2020 in English was conducted. Identified guidelines were screened for relevance to childhood glaucoma and exclusion criteria applied. Guidelines that passed the screening and quality appraisal with the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and, if they achieved a mean score of ≥45 and ≥3 on subsets of 9 and 5 AGREE II items, respectively, were selected for inclusion and data extracted using a standardised form. RESULTS: Following screening and critical appraisal, three guidelines were included for data extraction. None of the three guidelines was specifically developed for childhood glaucoma. A consistent recommendation was that children should undergo some form of eye screening examination or a comprehensive eye assessment to detect paediatric eye disease. Children at high risk of childhood glaucoma should undergo additional screening. One clinical practice guideline recommended interventions for childhood glaucoma consisting of tube surgery and topical beta-blockers or carbonic anhydrase inhibitors. Recommended interventions for childhood glaucoma were based on low-quality to moderate-quality evidence or expert opinion. CONCLUSION: Based on our selection criteria, we did not identify any high-quality clinical practice guidelines specifically targeted at childhood glaucoma. This is compounded by the lack of high-quality evidence on childhood glaucoma.

Advancing the Sustainable Development Goals through improving eye health: a scoping review.

UN member states have committed to achieving the Sustainable Development Goals (SDGs) by 2030. This Review examines the published evidence on how improving eye health can contribute to advancing the SDGs (beyond SDG 3). We identified 29 studies that showed direct benefits from providing eye health services on SDGs related to one or more of poverty (SDGs 1, 2, and 8), education (SDG 4), equality (SDGs 5 and 10), and sustainable cities (SDG 11). The eye health services included cataract surgery, free cataract screening, provision of spectacles, trichiasis surgery, rehabilitation services, and rural community eye health volunteers. These findings provide a comprehensive perspective on the direct links between eye health services and advancing the SDGs. In addition, eye health services likely have indirect effects on multiple SDGs, mediated through one of the direct effects. Finally, there are additional plausible links to other SDGs, for which evidence has not yet been established.

Intraocular lens optic edge design for the prevention of posterior capsule opacification after cataract surgery.

BACKGROUND: Posterior capsule opacification (PCO) is a clouding of the posterior part of the lens capsule, a skin-like transparent structure, which surrounds the crystalline lens in the human eye. PCO is the most common postoperative complication following modern cataract surgery with implantation of a posterior chamber intraocular lens (IOL). The main symptoms of PCO are a decrease in visual acuity, 'cloudy', blurred vision and reduced contrast sensitivity. PCO is treated with a neodymium:YAG (Nd:YAG) laser to create a small opening in the opaque capsule and regain a clear central visual axis. This capsulotomy might cause further ocular complications, such as raised intraocular pressure or swelling of the central retina (macular oedema). This procedure is also a significant financial burden for health care systems worldwide. In recent decades, there have been advances in the selection of IOL materials and optimisation of IOL designs to help prevent PCO formation after cataract surgery. These include changes to the side structures holding the lens in the centre of the lens capsule bag, called IOL haptics, and IOL optic edge designs. OBJECTIVES: To compare the effects of different IOL optic edge designs on PCO after cataract surgery. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Ovid Embase, Latin American and Caribbean Health Sciences Literature Database (LILACS), the ISRCTN registry, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 17 November 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared different types of IOL optic edge design. Our prespecified primary outcome was the proportion of eyes with Nd:YAG capsulotomy one year after surgery. Secondary outcomes included PCO score, best-corrected distance visual acuity (BCDVA) and quality of life score at one year. Due to availability of important long-term data, we also presented data at longer-term follow-up which is a post hoc change to our protocol. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane and the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 10 studies (1065 people, 1834 eyes) that compared sharp- and round-edged IOLs. Eight of these studies were within-person studies whereby one eye received a sharp-edged IOL and the fellow eye a round-edged IOL. The IOL materials were acrylic (2 studies), silicone (4 studies), polymethyl methacrylate (PMMA, 3 studies) and different materials (1 study). The studies were conducted in Austria, Germany, India, Japan, Sweden and the UK. Five studies were at high risk of bias in at least one domain. We judged two studies to be at low risk of bias in all domains. There were few cases of Nd:YAG capsulotomy at one year (primary outcome): 1/371 in sharp-edged and 4/371 in round-edged groups. The effect estimate was in favour of sharp-edged IOLs but the confidence intervals were very wide and compatible with higher or lower chance of Nd:YAG capsulotomy in sharp-edged compared with round-edged lenses (Peto odds ratio (OR) 0.30, 95% CI 0.05 to 1.74; I2 = 0%; 6 studies, 742 eyes). This corresponds to seven fewer cases of Nd:YAG capsulotomy per 1000 sharp-edged IOLs inserted compared with round-edged IOLs (95% CI 9 fewer to 7 more). We judged this as low-certainty evidence, downgrading for imprecision and risk of bias. A similar reduced risk of Nd:YAG capsulotomy in sharp-edge compared with round-edge IOLs was seen at two, three and five years but as the number of Nd:YAG capsulotomy events increased with longer follow-up this effect was more precisely measured at longer follow-up: two years, risk ratio (RR) 0.35 (0.16 to 0.80); 703 eyes (6 studies); 89 fewer cases per 1000; three years, RR 0.21 (0.11 to 0.41); 538 eyes (6 studies); 170 fewer cases per 1000; five years, RR 0.21 (0.10 to 0.45); 306 eyes (4 studies); 331 fewer cases per 1000. Data at 9 years and 12 years were only available from one study. All studies reported a PCO score. Four studies reported the AQUA (Automated Quantification of After-Cataract) score, four studies reported the EPCO (Evaluation of PCO) score and two studies reported another method of quantifying PCO. It was not possible to pool these data due to the way they were reported, but all studies consistently reported a statistically significant lower average PCO score (of the order of 0.5 to 3 units) with sharp-edged IOLs compared with round-edged IOLs. We judged this to be moderate-certainty evidence downgrading for risk of bias. The logMAR visual acuity score was lower (better) in eyes that received a sharp-edged IOL but the difference was small and likely to be clinically unimportant at one year (mean difference (MD) -0.06 logMAR, 95% CI -0.12 to 0; 2 studies, 153 eyes; low-certainty evidence). Similar effects were seen at longer follow-up periods but non-statistically significant data were less fully reported: two years MD -0.01 logMAR (-0.05 to 0.02); 2 studies, 311 eyes; three years MD -0.09 logMAR (-0.22 to 0.03); 2 studies, 117 eyes; data at five years only available from one study. None of the studies reported quality of life. Very low-certainty evidence on adverse events did not suggest any important differences between the groups. AUTHORS' CONCLUSIONS: This review provides evidence that sharp-edged IOLs are likely to be associated with less PCO formation than round-edged IOLs, with less Nd:YAG capsulotomy. The effects on visual acuity were less certain. The impact of these lenses on quality of life has not been assessed and there are only very low-certainty comparative data on adverse events.

Identifying priority review questions for Cochrane Eyes and Vision: protocol for a priority setting exercise.

INTRODUCTION: Cochrane Eyes and Vision (CEV) is an international network of individuals working to prepare, maintain and promote access to systematic reviews of interventions to treat, prevent or diagnose eye diseases or vision impairment. CEV plans to undertake a priority setting exercise to identify systematically research questions relevant to our scope, and to formally incorporate input from a wide range of stakeholders to set priorities for new and updated reviews. METHODS AND ANALYSIS: The scope of CEV is broad and our reviews include conditions that are common and have a high global disease burden, for example, cataract and dry eye disease, and conditions that are rare but have a high impact on quality of life and high individual cost such as eye cancer. We plan to focus on conditions prioritised by WHO during the development of the Package of Eye Care Interventions. These conditions were selected based on a combination of data on disease magnitude, healthcare use and expert opinion. We will identify priority review questions systematically by summarising relevant data on research in Eyes and Vision from a range of sources, and compiling a list of 10-15 potential review questions (new and/or updates) for each condition group. We will seek the views of external and internal stakeholders on this list by conducting an online survey. Equity will be a specific consideration. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee of the London School of Hygiene & Tropical Medicine. We will disseminate the findings through Cochrane channels and prepare a summary of the work for publication in a peer-reviewed journal.

Effectiveness of interventions to increase uptake and completion of treatment for diabetic retinopathy in low- and middle-income countries: a rapid review protocol.

BACKGROUND: Vision loss due to diabetic retinopathy can largely be prevented or delayed through treatment. Patients with vision-threatening diabetic retinopathy are typically offered laser or intravitreal injections which often require more than one treatment cycle. However, treatment is not always initiated, or it is not completed, resulting in poor visual outcomes. Interventions aimed at improving the uptake or completion of treatment for diabetic retinopathy can potentially help prevent or delay visual loss in people with diabetes. METHODS: We will search MEDLINE, Embase, Global Health and Cochrane Register of Studies for studies reporting interventions to improve the uptake of treatment for diabetic retinopathy (DR) and/or diabetic macular oedema (DMO), compared with usual care, in adults with diabetes. The review will include studies published in the last 20 years in the English language. We will include any study design that measured any of the following outcomes in relation to treatment uptake and completion for DR and/or DMO: (1) proportion of patients initiating treatment for DR and/or DMO among those to whom it is recommended, (2) proportion of patients completing treatment for DR and/or DMO among those to whom it is recommended, (3) proportion of patients completing treatment for DR and/or DMO among those initiating treatment and (4) number and proportion of DR and/or DMO rounds of treatment completed per patient, as dictated by the treatment protocol. For included studies, we will also report any measures of cost-effectiveness when available. Two reviewers will screen search results independently. Risk of bias assessment will be done by two reviewers, and data extraction will be done by one reviewer with verification of 10% of the papers by a second reviewer. The results will be synthesised narratively. DISCUSSION: This rapid review aims to identify and synthesise the peer-reviewed literature on the effectiveness of interventions to increase uptake and completion of treatment for DR and/or DMO in LMICs. The rapid review methodology was chosen in order to rapidly synthesise the available evidence to support programme implementers and policy-makers in designing evidence-based health programmes and public health policy and inform the allocation of resources. SYSTEMATIC REVIEW REGISTRATION: OSF osf.io/h5wgr.

Effectiveness of task-shifting for the detection of diabetic retinopathy in low- and middle-income countries: a rapid review protocol.

BACKGROUND: Diabetic retinopathy is the most common ocular complication of diabetes and a cause of vision loss in adults. Diabetic retinopathy screening leading to early identification of the disease followed by timely treatment, can prevent vision loss in people living with diabetes. A key barrier to the implementation of screening services in low- and middle-income countries is the low number of ophthalmologists per million population. Interventions that shift screening to non-ophthalmology cadres have been implemented in programmes in low- and middle-income countries and are routinely used in high-income countries. The aim of this rapid review is to summarise the published literature reporting the effectiveness of task-shifting interventions for the detection of diabetic retinopathy by non-ophthalmologists in low- and middle-income countries. METHODS: We will search MEDLINE, Embase, Global Health and Cochrane Register of Studies for studies reporting task-shifting interventions for diabetic retinopathy detection. The review will include studies published in the last 10 years in the English language. We will include any interventional or observational comparative study measuring outcomes in terms of participation or access to diabetic retinopathy detection services (uptake) and quality of diabetic retinopathy detection services (detection, severity, diagnostic accuracy). For included studies, cost-effectiveness of the task-shifting intervention will also be presented. Two reviewers will screen search results independently. The risk of bias assessment and data extraction will be carried out by one reviewer with verification of 10% of the papers by a second reviewer. The results will be synthesised narratively. DISCUSSION: Differences in health systems organization, structure and resources will determine the need and success of task-shifting interventions for DR screening. The review will examine how these interventions have been used and/or tested in LMICs. The results will be of interest to policy makers and programme managers tasked with designing and implementing services to prevent and manage diabetes and its complications in similar settings. SYSTEMATIC REVIEW REGISTRATION: OSF: https://osf.io/dfhg6/ .

Radiotherapy for neovascular age-related macular degeneration.

BACKGROUND: Radiotherapy has been proposed as a treatment for new vessel growth in people with neovascular age-related macular degeneration (AMD). OBJECTIVES: To examine the effects of radiotherapy on neovascular AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS and three trials registers and checked references of included studies. We last searched the databases on 4 May 2020.  SELECTION CRITERIA: We included all randomised controlled trials in which radiotherapy was compared to another treatment, sham treatment, low dosage irradiation or no treatment in people with choroidal neovascularisation (CNV) secondary to AMD. DATA COLLECTION AND ANALYSIS: We used standard procedures expected by Cochrane. We graded the certainty of the evidence using GRADE. We considered the following outcomes at 12 months: best-corrected visual acuity (BCVA) (loss of 3 or more lines, change in visual acuity), contrast sensitivity, new vessel growth, quality of life and adverse effects at any time point.  MAIN RESULTS: We included 18 studies (n = 2430 people, 2432 eyes) of radiation therapy with dosages ranging from 7.5 to 24 Gy. These studies mainly took place in Europe and North America but two studies were from Japan and one multicentre study included sites in South America. Three of these studies investigated brachytherapy (plaque and epimacular), the rest were studies of external beam radiotherapy (EBM) including one trial of stereotactic radiotherapy. Four studies compared radiotherapy combined with anti-vascular endothelial growth factor (anti-VEGF) with anti-VEGF alone. Eleven studies gave no radiotherapy treatment to the control group; five studies used sham irradiation; and one study used very low-dose irradiation (1 Gy). One study used a mixture of sham irradiation and no treatment. Fifteen studies were judged to be at high risk of bias in one or more domains. Radiotherapy versus no radiotherapy There may be little or no difference in loss of 3 lines of vision at 12 months in eyes treated with radiotherapy compared with no radiotherapy (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.64 to 1.04, 811 eyes, 8 studies, I2 = 66%, low-certainty evidence). Low-certainty evidence suggests a small benefit in change in visual acuity (mean difference (MD) -0.10 logMAR, 95% CI -0.17 to -0.03; eyes = 883; studies = 10) and average contrast sensitivity at 12 months (MD 0.15 log units, 95% CI 0.05 to 0.25; eyes = 267; studies = 2). Growth of new vessels (largely change in CNV size) was variably reported and It was not possible to produce a summary estimate of this outcome. The studies were small with imprecise estimates and there was no consistent pattern to the study results (very low-certainty evidence). Quality of life was only reported in one study of 199 people; there was no clear difference between treatment and control groups (low-certainty evidence). Low-certainty evidence was available on adverse effects from eight of 14 studies. Seven studies reported on radiation retinopathy and/or neuropathy. Five of these studies reported no radiation-associated adverse effects. One study of 88 eyes reported one case of possible radiation retinopathy. One study of 74 eyes graded retinal abnormalities in some detail and found that 72% of participants who had radiation compared with 71% of participants in the control group had retinal abnormalities resembling radiation retinopathy or choroidopathy. Four studies reported cataract surgery or progression: events were generally few with no consistent evidence of any increased occurrence in the radiation group. One study noted transient disturbance of the precorneal tear film but there was no evidence from the other two studies that reported dry eye of any increased risk with radiation therapy. None of the participants received anti-VEGF injections. Radiotherapy combined with anti-VEGF versus anti-VEGF alone People receiving radiotherapy/anti-VEGF were probably more likely to lose 3 or more lines of BCVA at 12 months compared with anti-VEGF alone (RR 2.11, 95% CI 1.40 to 3.17, 1050 eyes, 3 studies, moderate-certainty). Most of the data for this outcome come from two studies of epimacular brachytherapy (114 events) compared with 20 events from the one trial of EBM. Data on change in BCVA were heterogenous (I2 = 82%). Individual study results ranged from a small difference of -0.03 logMAR in favour of radiotherapy/anti-VEGF to a difference of 0.13 logMAR in favour of anti-VEGF alone (low-certainty evidence). The effect differed depending on how the radiotherapy was delivered (test for interaction P = 0.0007). Epimacular brachytherapy was associated with worse visual outcomes (MD 0.10 logMAR, 95% CI 0.05 to 0.15, 820 eyes, 2 studies) compared with EBM (MD -0.03 logMAR, 95% CI -0.09 to 0.03, 252 eyes, 2 studies). None of the included studies reported contrast sensitivity or quality of life. Growth of new vessels (largely change in CNV size) was variably reported in three studies (803 eyes). It was not possible to produce a summary estimate and there was no consistent pattern to the study results (very low-certainty evidence). For adverse outcomes, variable results were reported in the four studies. In three studies reports of adverse events were low and no radiation-associated adverse events were reported. In one study of epimacular brachytherapy there was a higher proportion of ocular adverse events (54%) compared to the anti-VEGF alone (18%). The majority of these adverse events were cataract. Overall 5% of the treatment group had radiation device-related adverse events (17 cases); 10 of these cases were radiation retinopathy. There were differences in average number of injections given between the four studies (1072 eyes). In three of the four studies, the anti-VEGF alone group on average received more injections (moderate-certainty evidence). AUTHORS' CONCLUSIONS: The evidence is uncertain regarding the use of radiotherapy for neovascular AMD. Most studies took place before the routine use of anti-VEGF, and before the development of modern radiotherapy techniques such as stereotactic radiotherapy. Visual outcomes with epimacular brachytherapy are likely to be worse, with an increased risk of adverse events,  probably related to vitrectomy. The role of stereotactic radiotherapy combined with anti-VEGF is currently uncertain. Further research on radiotherapy for neovascular AMD may not be justified until current ongoing studies have reported their results.

Outcomes in randomised controlled trials of multifocal lenses in cataract surgery: the case for development of a core outcome set.

BACKGROUND/AIMS: To describe and summarise the outcomes reported in randomised controlled trials of multifocal versus monofocal intraocular lenses in cataract surgery. METHODS: We identified all randomised controlled trials of multifocal versus monofocal lenses in a Cochrane review (last search date June 2016). We extracted and summarised data on all outcomes reported using the framework of domain, measurement, metric and method of aggregation. RESULTS: All studies collected data on distance and near visual acuity but there was considerable variation in the measures used and whether these outcomes were unaided or best corrected. Most studies reported final value measurements, rather than change from baseline. Approximately half of the studies reported data as a continuous measure only, one-third reported both continuous and categorical measures and a minority reported categorical measures only. There was little consensus as to cut-points. Although a majority of studies included one or more patient-reported outcome measures, none of the studies reported patient involvement in the choice of outcomes. CONCLUSION: The collection and analysis of data on outcome measures in studies of multifocal intraocular lenses in cataract surgery are complicated. As a result, there is considerable heterogeneity in collection and reporting in the medical literature. This makes it difficult to synthesise such data to provide robust estimates of effect and is a potential source of research waste. Investigators in this field must produce a core outcome set that is informed by patients' views and we propose an initial set of outcomes on which these could be based.

Toric intraocular lens versus limbal relaxing incisions for corneal astigmatism after phacoemulsification.

BACKGROUND: Cataract is the leading cause of blindness in the world, and clinically significant astigmatism may affect up to approximately 20% of people undergoing cataract surgery. Pre-existing astigmatism in people undergoing cataract surgery may be treated, among other techniques, by placing corneal incisions near the limbus (limbal relaxing incisions or LRIs) or by toric intraocular lens (IOLs) specially designed to reduce or treat the effect of corneal astigmatism on unaided visual acuity. OBJECTIVES: To assess the effects of toric IOLs compared with LRIs in the management of astigmatism during phacoemulsification cataract surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2019, Issue 9); Ovid MEDLINE; Ovid Embase and four other databases. The date of the search was 27 September 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing toric IOLs with LRIs during phacoemulsification cataract surgery.  DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We graded the certainty of the evidence using GRADE. Our primary outcome was the proportion of participants with postoperative residual refractive astigmatism of less than 0.50 dioptres (D) six months or more after surgery. We also collected data on mean residual refractive astigmatism. Secondary outcomes included: uncorrected distance visual acuity, vision-related quality of life, spectacle independence and adverse effects including postoperative lens rotation requiring re-alignment. To supplement the main systematic review assessing the effects of toric IOLs compared with LRIs in the management of astigmatism during phacoemulsification cataract surgery, we sought to identify economic evaluations on the subject. MAIN RESULTS: We identified 10 relevant studies including 517 people (626 eyes). These studies took place in China (three studies), UK (three), Brazil (one), India (one), Italy (one) and Spain (one). The median age of participants was 71 years. The level of corneal astigmatism specified in the inclusion criteria of these studies ranged from 0.75 D to 3 D. A variety of toric IOLs were used in these studies, in all but one study, these were monofocal. Studies used three different nomograms to determine the size and placement of the LRI. Two studies did not specify this. None of the studies were at low risk of bias in all domains, but two studies were at low risk of bias in all domains except selective outcome reporting, which was unclear. The remaining studies were at a mixture of low, unclear or high risk of bias. People receiving toric IOLs were probably more likely to achieve a postoperative residual refractive astigmatism of less than 0.5 D six months or more after surgery (risk ratio (RR) 1.40, 95% confidence interval (CI) 1.10 to 1.78; 5 RCTs, 262 eyes). We judged this to be moderate-certainty evidence, downgrading for risk of bias. In the included studies, approximately 500 eyes per 1000 achieved postoperative astigmatism less than 0.5 D in the LRI group compared with 700 per 1000 in the toric IOLs group. There was a small difference in residual astigmatism between the two groups, favouring toric IOLs (mean difference (MD) -0.32 D, 95% CI -0.48 to -0.15 D; 10 RCTs, 620 eyes). Although all studies favoured toric IOLs, the results of individual studies were inconsistent (range of effects -0.02 D to -0.71 D; I² = 89%). We considered this to be low-certainty evidence, downgrading for risk of bias and inconsistency. People receiving a toric IOL probably have a small improvement in visual acuity at six months or more after surgery compared to people receiving LRI, but the difference is small and probably clinically insignificant (MD -0.04 logMAR, 95% CI -0.07 to -0.02; 8 RCTs, 474 eyes; moderate-certainty evidence). Low-certainty evidence from one study of 40 people suggested little difference in vision-related quality of life measured using the Visual Function Index (VF-14) (MD -3.01, 95% CI -8.56 to 2.54). Two studies reported spectacle independence and suggested that people receiving toric IOLs may be more likely to be spectacle independent (RR 1.56, 95% CI 1.14 to 2.15; 100 people; low-certainty evidence). There were no cases of lens rotation requiring surgery (very low-certainty evidence). Five studies (320 eyes) commented on a range of other adverse effects including corneal oedema, endophthalmitis and corneal ectasia. All these studies reported that there were no adverse events with the exception of one study (40 eyes) where one participant in the LRI group had a central de-epithelisation which recovered over 10 days. We found no economic studies that compared toric IOLs with LRIs. AUTHORS' CONCLUSIONS: Toric IOLs probably provide a higher chance of achieving astigmatism within 0.5 D after cataract surgery compared with LRIs. There may be a small mean difference in postoperative astigmatism, favouring toric IOLs, but this difference is likely to be clinically unimportant. There was no evidence of an important difference in postoperative visual acuity or quality of life between the techniques. Evidence on adverse effects was uncertain. The apparent shortage of relevant economic evaluations indicates that economic evidence regarding the costs and consequence of these two procedures is currently lacking.

Antibiotics for trachoma.

BACKGROUND: Trachoma is the world's leading infectious cause of blindness. In 1996, WHO launched the Alliance for the Global Elimination of Trachoma by the year 2020, based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness, and environmental improvement). OBJECTIVES: To assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective), Chlamydia trachomatis infection of the conjunctiva, antibiotic resistance, and adverse effects (secondary objectives). SEARCH METHODS: We searched relevant electronic databases and trials registers. The date of the last search was 4 January 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people or communities with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people or communities with trachoma. We also included studies addressing different dosing strategies in the population.  DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified 14 studies where individuals with trachoma were randomised and 12 cluster-randomised studies. Any antibiotic versus control (individuals)Nine studies (1961 participants) randomised individuals with trachoma to antibiotic or control (no treatment or placebo). All of these studies enrolled children and young people with active trachoma. The antibiotics used in these studies included topical (oxy)tetracycline (5 studies), doxycycline (2 studies), and sulfonamides (4 studies). Four studies had more than two study arms. In general these studies were poorly reported, and it was difficult to judge risk of bias.These studies provided low-certainty evidence that people with active trachoma treated with antibiotics experienced a reduction in active trachoma at three months (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69 to 0.89; 1961 people; 9 RCTs; I2 = 73%) and 12 months (RR 0.74, 95% CI 0.55 to 1.00; 1035 people; 4 RCTs; I2 = 90%). Low-certainty evidence was available for ocular infection at three months (RR 0.81, 95% CI 0.63 to 1.04; 297 people; 4 RCTs; I2 = 0%) and 12 months (RR 0.25, 95% CI 0.08 to 0.78; 129 people; 1 RCT). None of these studies assessed antimicrobial resistance. In those studies that reported harms, no serious adverse effects were reported (low-certainty evidence).Oral versus topical antibiotics (individuals)Eight studies (1583 participants) compared oral and topical antibiotics. Only one study included people older than 21 years of age. Oral antibiotics included azithromycin (5 studies), sulfonamides (2 studies), and doxycycline (1 study). Topical antibiotics included (oxy)tetracycline (6 studies), azithromycin (1 study), and sulfonamide (1 study). These studies were poorly reported, and it was difficult to judge risk of bias.There was low-certainty evidence of little or no difference in effect between oral and topical antibiotics on active trachoma at three months (RR 0.97, 95% CI 0.81 to 1.16; 953 people; 6 RCTs; I2 = 63%) and 12 months (RR 0.93, 95% CI 0.75 to 1.15; 886 people; 5 RCTs; I2 = 56%). There was very low-certainty evidence for ocular infection at three or 12 months. Antimicrobial resistance was not assessed. In those studies that reported adverse effects, no serious adverse effects were reported; one study reported abdominal pain with azithromycin; one study reported a couple of cases of nausea with azithromycin; and one study reported three cases of reaction to sulfonamides (low-certainty evidence).Oral azithromycin versus control (communities)Four cluster-randomised studies compared antibiotic with no or delayed treatment. Data were available on active trachoma at 12 months from two studies but could not be pooled because of reporting differences. One study at low risk of bias found a reduced prevalence of active trachoma 12 months after a single dose of azithromycin in communities with a high prevalence of infection (RR 0.58, 95% CI 0.52 to 0.65; 1247 people). The other, lower quality, study in low-prevalence communities reported similar median prevalences of infection at 12 months: 9.3% in communities treated with azithromycin and 8.2% in untreated communities. We judged this moderate-certainty evidence for a reduction in active trachoma with treatment, downgrading one level for inconsistency between the two studies. Two studies reported ocular infection at 12 months and data could be pooled. There was a reduction in ocular infection (RR 0.36, 0.31 to 0.43; 2139 people) 12 months after mass treatment with a single dose compared with no treatment (moderate-certainty evidence). There was high-certainty evidence of an increased risk of resistance of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli to azithromycin, tetracycline, and clindamycin in communities treated with azithromycin, with approximately 5-fold risk ratios at 12 months. The evidence did not support increased resistance to penicillin or trimethoprim-sulfamethoxazole. None of the studies measured resistance to C trachomatis. No serious adverse events were reported. The main adverse effect noted for azithromycin (˜10%) was abdominal pain, vomiting, and nausea.Oral azithromycin versus topical tetracycline (communities)Three cluster-randomised studies compared oral azithromycin with topical tetracycline. The evidence was inconsistent for active trachoma and ocular infection at three and 12 months (low-certainty evidence) and was not pooled due to considerable heterogeneity. Antimicrobial resistance and adverse effects were not reported.Different dosing strategiesSix studies compared different strategies for dosing. There were: mass treatment at different dosing intervals; applying cessation or stopping rules to mass treatment; strategies to increase mass treatment coverage. There was no strong evidence to support any variation in the recommended annual mass treatment. AUTHORS' CONCLUSIONS: Antibiotic treatment may reduce the risk of active trachoma and ocular infection in people infected with C trachomatis, compared to no treatment/placebo, but the size of the treatment effect in individuals is uncertain. Mass antibiotic treatment with single dose oral azithromycin reduces the prevalence of active trachoma and ocular infection in communities. There is no strong evidence to support any variation in the recommended periodicity of annual mass treatment. There is evidence of an increased risk of antibiotic resistance at 12 months in communities treated with antibiotics.

Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis.

BACKGROUND: Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. OBJECTIVES: The 2014 update of this review found high-quality evidence of benefit with anti-VEGF modalities, compared to laser photocoagulation, for the treatment of DMO. The objective of this updated review is to compare the effectiveness and safety of the different anti-VEGF drugs using network meta-analysis methods. SEARCH METHODS: We searched various electronic databases on 26 April 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham or no treatment in people with DMO. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for pair-wise meta-analysis and we augmented this evidence using network meta-analysis methods. We focused on the relative efficacy and safety of the three most commonly used drugs as interventions of direct interest for practice: aflibercept and ranibizumab, used on-label; and off-label bevacizumab.We collected data on three efficacy outcomes (gain of 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters; mean change in best-corrected visual acuity (BCVA); mean change in central retinal thickness (CRT)), three safety outcomes (all severe systemic adverse events (SSAEs); all-cause death; arterial thromboembolic events) and quality of life.We used Stata 'network' meta-analysis package for all analyses. We investigated the risk of bias of mixed comparisons based on the variance contribution of each study, having assigned an overall risk of bias to each study. MAIN RESULTS: Twenty-four studies included 6007 participants with DMO and moderate vision loss, of which two studies randomised 265 eyes of 230 participants and one was a cross-over study on 56 participants (62 eyes) that was treated as a parallel-arm trial. Data were collected on drugs of direct interest from three studies on aflibercept (975 eyes), eight studies on bevacizumab (515 eyes), and 14 studies on ranibizumab (1518 eyes). As treatments of indirect interest or legacy treatment we included three studies on pegaptanib (541 eyes), five studies on ranibizumab plus prompt laser (557 eyes), one study on ranibizumab plus deferred laser (188 eyes), 13 studies on laser photocoagulation (936 eyes) and six studies on sham treatment (793 eyes).Aflibercept, bevacizumab and ranibizumab were all more effective than laser for improving vision by 3 or more lines after one year (high-certainty evidence). Approximately one in 10 people improve vision with laser, and about three in 10 people improve with anti-VEGF treatment: risk ratio (RR) versus laser 3.66 (95% confidence interval (CI) 2.79 to 4.79) for aflibercept; RR 2.47 (95% CI 1.81 to 3.37) for bevacizumab; RR 2.76 (95% CI 2.12 to 3.59) for ranibizumab. On average there was no change in visual acuity (VA) with laser after one year, compared with a gain of 1 or 2 lines with anti-VEGF treatment: laser versus aflibercept mean difference (MD) -0.20 (95% CI -0.22 to -0.17) logMAR; versus bevacizumab MD -0.12 (95% CI -0.15 to -0.09) logMAR; versus ranibizumab MD -0.12 (95% CI -0.14 to -0.10) logMAR. The certainty of the evidence was high for the comparison of aflibercept and ranibizumab with laser and moderate for bevacizumab comparison with laser due to inconsistency between the indirect and direct evidence.People receiving ranibizumab were less likely to gain 3 or more lines of VA at one year compared with aflibercept: RR 0.75 (95% CI 0.60 to 0.94), moderate-certainty evidence. For every 1000 people treated with aflibercept, 92 fewer would gain 3 or more lines of VA at one year if treated with ranibizumab (22 to 148 fewer). On average people receiving ranibizumab had worse VA at one year (MD 0.08 logMAR units, 95% CI 0.05 to 0.11), moderate-certainty evidence; and higher CRT (MD 39 µm, 95% CI 2 µm to 76 µm; low-certainty evidence). Ranibizumab and bevacizumab were comparable with respect to aflibercept and did not differ in terms of VA: RR of gain of 3 or more lines of VA at one year 1.11 (95% CI 0.87 to 1.43), moderate-certainty evidence, and difference in change in VA was 0.00 (95% CI -0.02 to 0.03) logMAR, moderate-certainty evidence. CRT reduction favoured ranibizumab by -29 µm (95% CI -58 µm to -1 µm, low-certainty evidence). There was no evidence of overall statistical inconsistency in our analyses.The previous version of this review found moderate-certainty evidence of good safety of antiangiogenic drugs versus control. This update used data at the longest available follow-up (one or two years) and found that aflibercept, ranibizumab and bevacizumab do not differ regarding systemic serious adverse events (SSAEs) (moderate- or high-certainty evidence). However, risk of bias was variable, loop inconsistency could be found and estimates were not precise enough on relative safety regarding less frequent events such as arterial thromboembolic events or death (low- or very low-certainty evidence).Two-year data were available and reported in only four RCTs in this review. Most industry-sponsored studies were open-label after one year. One large publicly-funded study compared the three drugs at two years and found no difference. AUTHORS' CONCLUSIONS: Anti-VEGF drugs are effective at improving vision in people with DMO with three to four in every 10 people likely to experience an improvement of 3 or more lines VA at one year. Aflibercept may confer some advantage over ranibizumab and bevacizumab in people with DMO at one year in visual and anatomic terms but it is unclear whether this applies to the long-term. There is a need for more evidence on the long-term (greater than two years) comparative effects of these anti-VEGF agents. Evidence from RCTs may not apply to real-world practice, where people in need of antiangiogenic treatment are often under-treated and under-monitored.We found no signals of differences in overall safety between the three antiangiogenic drugs that are currently available to treat DMO, but our estimates are imprecise for cardiovascular events and death.

Different lasers and techniques for proliferative diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a chronic progressive disease of the retinal microvasculature associated with prolonged hyperglycaemia. Proliferative DR (PDR) is a sight-threatening complication of DR and is characterised by the development of abnormal new vessels in the retina, optic nerve head or anterior segment of the eye. Argon laser photocoagulation has been the gold standard for the treatment of PDR for many years, using regimens evaluated by the Early Treatment of Diabetic Retinopathy Study (ETDRS). Over the years, there have been modifications of the technique and introduction of new laser technologies. OBJECTIVES: To assess the effects of different types of laser, other than argon laser, and different laser protocols, other than those established by the ETDRS, for the treatment of PDR. We compared different wavelengths; power and pulse duration; pattern, number and location of burns versus standard argon laser undertaken as specified by the ETDRS. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 5); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 8 June 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of pan-retinal photocoagulation (PRP) using standard argon laser for treatment of PDR compared with any other laser modality. We excluded studies of lasers that are not in common use, such as the xenon arc, ruby or Krypton laser. DATA COLLECTION AND ANALYSIS: We followed Cochrane guidelines and graded the certainty of evidence using the GRADE approach. MAIN RESULTS: We identified 11 studies from Europe (6), the USA (2), the Middle East (1) and Asia (2). Five studies compared different types of laser to argon: Nd:YAG (2 studies) or diode (3 studies). Other studies compared modifications to the standard argon laser PRP technique. The studies were poorly reported and we judged all to be at high risk of bias in at least one domain. The sample size varied from 20 to 270 eyes but the majority included 50 participants or fewer.Nd:YAG versus argon laser (2 studies): very low-certainty evidence on vision loss, vision gain, progression and regression of PDR, pain during laser treatment and adverse effects.Diode versus argon laser (3 studies): very-low certainty evidence on vision loss, vision gain, progression and regression of PDR and adverse effects; moderate-certainty evidence that diode laser was more painful (risk ratio (RR) troublesome pain during laser treatment (RR 3.12, 95% CI 2.16 to 4.51; eyes = 202; studies = 3; I2 = 0%).0.5 second versus 0.1 second exposure (1 study): low-certainty evidence of lower chance of vision loss with 0.5 second compared with 0.1 second exposure but estimates were imprecise and compatible with no difference or an increased chance of vision loss (RR 0.42, 95% CI 0.08 to 2.04, 44 eyes, 1 RCT); low-certainty evidence that people treated with 0.5 second exposure were more likely to gain vision (RR 2.22, 95% CI 0.68 to 7.28, 44 eyes, 1 RCT) but again the estimates were imprecise . People given 0.5 second exposure were more likely to have regression of PDR compared with 0.1 second laser PRP again with imprecise estimate (RR 1.17, 95% CI 0.92 to 1.48, 32 eyes, 1 RCT). There was very low-certainty evidence on progression of PDR and adverse effects.'Light intensity' PRP versus classic PRP (1 study): vision loss or gain was not reported but the mean difference in logMAR acuity at 1 year was -0.09 logMAR (95% CI -0.22 to 0.04, 65 eyes, 1 RCT); and low-certainty evidence that fewer patients had pain during light PRP compared with classic PRP with an imprecise estimate compatible with increased or decreased pain (RR 0.23, 95% CI 0.03 to 1.93, 65 eyes, 1 RCT).'Mild scatter' (laser pattern limited to 400 to 600 laser burns in one sitting) PRP versus standard 'full' scatter PRP (1 study): very low-certainty evidence on vision and visual field loss. No information on adverse effects.'Central' (a more central PRP in addition to mid-peripheral PRP) versus 'peripheral' standard PRP (1 study): low-certainty evidence that people treated with central PRP were more likely to lose 15 or more letters of BCVA compared with peripheral laser PRP (RR 3.00, 95% CI 0.67 to 13.46, 50 eyes, 1 RCT); and less likely to gain 15 or more letters (RR 0.25, 95% CI 0.03 to 2.08) with imprecise estimates compatible with increased or decreased risk.'Centre sparing' PRP (argon laser distribution limited to 3 disc diameters from the upper temporal and lower margin of the fovea) versus standard 'full scatter' PRP (1 study): low-certainty evidence that people treated with 'centre sparing' PRP were less likely to lose 15 or more ETDRS letters of BCVA compared with 'full scatter' PRP (RR 0.67, 95% CI 0.30 to 1.50, 53 eyes). Low-certainty evidence of similar risk of regression of PDR between groups (RR 0.96, 95% CI 0.73 to 1.27, 53 eyes). Adverse events were not reported.'Extended targeted' PRP (to include the equator and any capillary non-perfusion areas between the vascular arcades) versus standard PRP (1 study): low-certainty evidence that people in the extended group had similar or slightly reduced chance of loss of 15 or more letters of BCVA compared with the standard PRP group (RR 0.94, 95% CI 0.70 to 1.28, 270 eyes). Low-certainty evidence that people in the extended group had a similar or slightly increased chance of regression of PDR compared with the standard PRP group (RR 1.11, 95% CI 0.95 to 1.31, 270 eyes). Very low-certainty information on adverse effects. AUTHORS' CONCLUSIONS: Modern laser techniques and modalities have been developed to treat PDR. However there is limited evidence available with respect to the efficacy and safety of alternative laser systems or strategies compared with the standard argon laser as described in ETDRS.

Community screening for visual impairment in older people.

BACKGROUND: Visual problems in older people are common and frequently under-reported. The effects of poor vision in older people are wide reaching and include falls, confusion and reduced quality of life. Much of the visual impairment in older ages can be treated (e.g. cataract surgery, correction of refractive error). Vision screening may therefore reduce the number of older people living with sight loss. OBJECTIVES: The objective of this review was to assess the effects on vision of community vision screening of older people for visual impairment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 23 November 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared vision screening alone or as part of a multi-component screening package as compared to no vision screening or standard care, on the vision of people aged 65 years or over in a community setting. We included trials that used self-reported visual problems or visual acuity testing as the screening tool. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We graded the certainty of the evidence using GRADE. MAIN RESULTS: Visual outcome data were available for 10,608 people in 10 trials. Four trials took place in the UK, two in Australia, two in the United States and two in the Netherlands. Length of follow-up ranged from one to five years. Three of these studies were cluster-randomised trials whereby general practitioners or family physicians were randomly allocated to undertake vision screening or no vision screening. All studies were funded by government agencies. Overall we judged the studies to be at low risk of bias and only downgraded the certainty of the evidence (GRADE) for imprecision.Seven trials compared vision screening as part of a multi-component screening versus no screening. Six of these studies used self-reported vision as both screening tool and outcome measure, but did not directly measure vision. One study used a combination of self-reported vision and visual acuity measurement: participants reporting vision problems at screening were treated by the attending doctor, referred to an eye care specialist or given information about resources that were available to assist with poor vision. There was a similar risk of "not seeing well" at follow-up in people screened compared with people not screened in meta-analysis of six studies (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.97 to 1.14, 4522 participants high-certainty evidence). One trial reported "improvement in vision" and this occurred slightly less frequently in the screened group (RR 0.85, 95% CI 0.52 to 1.40, 230 participants, moderate-certainty evidence).Two trials compared vision screening (visual acuity testing) alone with no vision screening. In one study, distance visual acuity was similar in the two groups at follow-up (mean difference (MD) 0.02 logMAR, 95% CI -0.02 to 0.05, 532 participants, high-certainty evidence). There was also little difference in near acuity (MD 0.02 logMAR, 95% CI -0.03 to 0.07, 532 participants, high-certainty evidence). There was no evidence of any important difference in quality of life (MD -0.06 National Eye Institute 25-item visual function questionnaire (VFQ-25) score adjusted for baseline VFQ-25 score, 95% CI -2.3 to 1.1, 532 participants, high-certainty evidence). The other study could not be included in the data analysis as the number of participants in each of the arms at follow-up could not be determined. However the authors stated that there was no significant difference in mean visual acuity in participants who had visual acuity assessed at baseline (39 letters) as compared to those who did not have their visual acuity assessed (35 letters, P = 0.25, 121 participants).One trial compared a detailed health assessment including measurement of visual acuity (intervention) with a brief health assessment including one question about vision (standard care). People given the detailed health assessment had a similar risk of visual impairment (visual acuity worse than 6/18 in either eye) at follow-up compared with people given the brief assessment (RR 1.07, 95% CI 0.84 to 1.36, 1807 participants, moderate-certainty evidence). The mean composite score of the VFQ-25 was 86.0 in the group that underwent visual acuity screening compared with 85.6 in the standard care group, a difference of 0.40 (95% CI -1.70 to 2.50, 1807 participants, high-certainty evidence). AUTHORS' CONCLUSIONS: The evidence from RCTs undertaken to date does not support vision screening for older people living independently in a community setting, whether in isolation or as part of a multi-component screening package. This is true for screening programmes involving questions about visual problems, or direct measurements of visual acuity.The most likely reason for this negative review is that the populations within the trials often did not take up the offered intervention as a result of the vision screening and large proportions of those who did not have vision screening appeared to seek their own intervention. Also, trials that use questions about vision have a lower sensitivity and specificity than formal visual acuity testing. Given the importance of visual impairment among older people, further research into strategies to improve vision of older people is needed. The effectiveness of an optimised primary care-based screening intervention that overcomes possible factors contributing to the observed lack of benefit in trials to date warrants assessment; trials should consider including more dependent participants, rather than those living independently in the community.