Technologies for the diagnosis of angle closure glaucoma (ACE): protocol of a prospective, multicentre, cross-sectional diagnostic study.

INTRODUCTION: Angle-closure is responsible for half of all glaucoma blindness globally. Patients with suspected glaucoma require assessment of the drainage angle by an experienced clinician. The goal of this study is to evaluate the diagnostic performance and cost-effectiveness of two non-contact tests, anterior segment OCT (Optical Coherence Tomography) (AS-OCT) and limbal anterior chamber depth for patients referred to hospital with suspected angle closure compared with gonioscopy by ophthalmologist. METHODS AND ANALYSIS: Study design: prospective, multicentre, cross-sectional diagnostic accuracy study. INCLUSION CRITERIA: adults referred from community optometry to hospital with suspected angle closure. PRIMARY OUTCOME: Sensitivity and specificity. SECONDARY OUTCOMES: Positive/negative likelihood ratios, concordance, cost-effectiveness, proportion of patients requiring subsequent clinical assessment by ophthalmologist. SAMPLE SIZE: 600 individuals who have been referred with suspected angle closure from primary care (community optometry). We will have a 95% probability of detecting the true sensitivity of either test to within ±3.5% based on a sensitivity of 90%. The study would also have a 95% probability of detecting the true specificity of either test to within ±5%, assuming a specificity of 75%. ETHICS AND DISSEMINATION: Ethical Review Board approval was obtained. REC reference: 22/LO/0885. Our findings will be disseminated to those involved in eye care services. We will have a knowledge exchange event at the end of the study, published via the Health Technology Assessment web page and in specialist journals. The results will be presented at professional conferences and directly to patients via patient group meetings and the Glaucoma UK charity. TRIAL REGISTRATION NUMBER: ISRCTN15115867.

Microperimetry assessment in foveal hypoplasia: functional results in a series of pediatric patients.

OBJECTIVE: To study the relationships of functional and morphologic retinal parameters in a series of pediatric patients with varying degrees of foveal hypoplasia (FH). DESIGN: Monocentric observational retrospective study. PARTICIPANTS: Among 21 pediatric patients, 16 met inclusion criteria, having FH confirmed with spectral-domain optical coherence tomography (SD-OCT) scan METHODS: Data were analyzed retrospectively. Patients able to undergo macular microperimetry (MP) and SD-OCT examinations were included in the analysis. MP and SD-OCT outcomes were compared with FH grading and best-corrected visual acuity (BCVA) using Pearson's correlation. RESULTS: Thirty-one eyes from 16 patients (mean age 12.4 years) with different degrees of FH were analyzed. Two patients had grade 1, 7 had grade 2, 5 had grade 3, and 2 had grade 4 FH. Clinical nystagmus was present in 8 patients. The correlation between BCVA and SD-OCT data (-0.31) was lower than that found between BCVA and nystagmus (0.64), that for fixation index P1 (-0.60), as well as that for macular sensitivity (-0.63). CONCLUSIONS: Although limited by the small sample, our study confirms the feasibility of automated MP evaluation in pediatric patients with FH. The added value of this work is the provision of data on relationships between anatomic and functional macular measurements acquired with SD-OCT, MP, and BCVA in eyes with various degrees of FH. Larger prospective studies are necessary to confirm these results.

Assessment of intravitreal anti-VEGF drugs and dexamethasone for retinal diseases in real world setting: A multi-centre prospective study from Southern Italy.

Describe drug utilisation and clinical outcomes of intravitreal anti-VEGF drug and dexamethasone use in the real-world setting in Southern Italy using data from multi-centre study of retinal disease. Clinical data of retinal disease patients treated with anti-VEGF drugs and dexamethasone implant in 6 out-patient ophthalmology centres from Southern Italy were collected by means of an electronic case report form. Patients receiving at least one intravitreal injection/implant of the study drugs were followed for up to two years and described in terms of demographics and clinical characteristics. Drug utilisation patterns were described. A sign-rank test was used to compare clinical data on visual acuity and other ophthalmic parameters from baseline at different follow-up times for each indication. Data from 1327 patients was collected. Most patients were diagnosed with age-related macular degeneration (AMD) (660, 49.7%), followed by diabetic macular oedema (423, 31.9%), retinal vein occlusion (164, 12.3%), and myopic choroidal neovascularization (80, 6.0%). Patients were followed for a median of 10.3 months (interquartile range: 3.6 - 24.7 months). Mean patient age was 69.7 (±10.9) years and 54.2% were males. Ranibizumab (55.4%) and aflibercept (27.5%) were the most commonly used drugs. Baseline visual acuity significantly improved by about 0.05 to 0.1 logMAR at all follow-up times for AMD and RVO but less consistently for the other diseases. Intravitreal ranibizumab use accounted for half of all treatment for retinal diseases in a Southern Italian out-patient setting. Patients treated with anti-VEGF drugs for AMD and RVO in Southern Italy experienced significant improvement in VA.

Cost analysis of eye bank versus surgeon prepared endothelial grafts.

BACKGROUND: Selective lamellar corneal transplantation (keratoplasty) has overtaken full thickness penetrating keratoplasty as the graft choice for endothelial failure. Even more recently eye bank prepared tissues are becoming increasing popular as a way to reduce the risks of tissue loss and stress during endothelial keratoplasty preparation in the surgical theatre. This study compares costs between surgeon and eye bank prepared tissues for Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK). METHODS: Retrospective study conducted at the Royal Liverpool University Hospital including endothelial keratoplasties with a minimum of 6 months follow-up time. Cost analysis included surgical expenses, tissue acquisition fees, cost of patient's ward admission and out-patient expenses, including cost of re-bubbling procedures, costs of visits, anterior segment imaging and optometrist visits within the first 6 months follow-up. RESULTS: Ninety-eight eyes of 98 patients were included in the study of which 42 underwent DSAEK surgery and 56 DMEK surgery. Cost analysis of surgical expenses in the DSAEK group showed a significant difference between using surgeon prepared and eye bank prepared tissue (£3866 ± 296 and £4389 ± 360, respectively; p < 0.01) and the same was found in the DMEK group (£3682 ± 167 and £4162 ± 167 for surgeon prepared and eye bank prepared tissues, respectively; p < 0.01). Cost of out-patient visits did not differ significantly in either group. CONCLUSIONS: At the Royal Liverpool University Hospital, eye bank prepared tissues had higher surgical expenses compared to those prepared by the surgeon, while the post-operative care expenses were similar between the two groups.

The Role of OCT Angiography in the Assessment of Epiretinal Macular Membrane.

BACKGROUND: The aim of this observational study is to assess pre- and postoperative retinochoroidal vascular changes in patients undergoing epiretinal macular membrane (ERM) surgery by using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: 23 eyes affected by ERM and those which underwent phacovitrectomy associated with ERM peeling were enrolled. They were evaluated using structural OCT and OCTA before surgery and at 1, 3, and 6 months postoperatively. RESULTS: We found a statistically significant (p < 0.05) increase in the superficial capillary plexus vessel density (VD) from baseline to the 6-month follow-up. We observed a large increase in both the perfusion density (PD) and the VD of the deep capillary plexus between baseline and the 6-month follow-up (p < 0.001). A significant decrease in the VD and PD of the choriocapillaris (CC) from baseline to the 1st month and a significant increase in CC perfusion density at the 6-month follow-up compared to the preoperative value were revealed. The FAZ area and perimeter after surgery significantly increased during the follow-up (p < 0.001) at baseline retinal and choroidal plexi with a lower PD or VD correlated with worse visual acuity (p < 0.05 for all plexi). At baseline and at the 1-month follow-up, a significant correlation was found with the FAZ area and the FAZ perimeter: a smaller FAZ area or a smaller FAZ perimeter was correlated to a lower visual acuity. Before surgery, negative correlations (p < 0.05) were found between the Govetto ERM stages and perfusion density of the SCP and the DCP and between the Govetto stages and vessel density of the DCP. CONCLUSIONS: In our study, OCTA detected vascular alterations induced by the presence of the ERM, allowing several correlations with functional data. In these patients, OCTA may be useful to add new potential surgical prognostic factors.

Saccadic movements assessment in eccentric fixation: A study in patients with Stargardt disease.

PURPOSE: To investigate saccadic movements in subjects with eccentric fixation due to a deep central scotoma in Stargardt disease (STGD). METHODS: We studied 10 patients with STGD and 10 healthy subjects (control group). Saccadic movements of all the 20 subjects were assessed by using the eye tracker technique Tobii Glasses Pro 2. Standard measurements of reading ability (MNREAD charts), visual acuity (ETDRS charts), contrast sensitivity (Pelli-Robson charts), reading contrast threshold and speed (REX charts), retinal sensitivity and stability and localization of the fixation (MP1 fundus perimetry) were obtained in all subjects. RESULTS: The saccadic movements time was significantly slower in STGD than in healthy subjects (699 ± 193 ms vs 299 ± 40 ms, p < 0.001). When STGD patients moved fixation to the target localized in retinal scotomatous areas, the movement was significantly slower compared to non scotomatous areas in the retina (1103 ± 798 ms vs 524 ± 187 ms, p = 0.039). There was a trend toward a correlation between slow saccadic movements in STGD subjects and the reading performance indices, although statistical significance was not achieved. CONCLUSION: Ocular saccades guided by eccentric fixation in STGD patients are significantly slower than in the control group, especially when the target corresponds to retinal areas with a deep scotoma. These results can explain the worse reading performance in STGD subjects, in particular when a non-viewing area on the right part of the text is present.

Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of permanent blindness worldwide. The current mainstay of treatment for neovascular AMD (nAMD) is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents: aflibercept, ranibizumab, and off-label bevacizumab. Injections can be given monthly, every two or three months ('extended-fixed'), or as needed (pro re nata (PRN)). A variant of PRN is 'treat-and-extend' whereby injections are resumed if recurrence is detected and then delivered with increasing intervals. Currently, injection frequency varies among practitioners, which underscores the need to characterize an optimized approach to nAMD management. OBJECTIVES: To investigate the effects of monthly versus non-monthly intravitreous injection of an anti-VEGF agent in people with newly diagnosed nAMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers from 2004 to October 2019; checked references; handsearched conference abstracts; and contacted pharmaceutical companies to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared different treatment regimens for anti-VEGF agents in people with newly diagnosed nAMD. We considered standard doses only (ranibizumab 0.5 mg, bevacizumab 1.25 mg, aflibercept 2.0 mg, or a combination of these). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for trial selection, data extraction, and analysis. MAIN RESULTS: We included 15 RCTs. The total number of participants was 7732, ranging from 37 to 2457 in each trial. The trials were conducted worldwide. Of these, six trials exclusively took place in the US, and three included centers from more than one country. Eight trials were at high risk of bias for at least one domain and all trials had at least one domain at unclear risk of bias. Seven trials (3525 participants) compared a PRN regimen with a monthly injection regimen, of which five trials delivered four to eight injections using standard PRN and three delivered nine or 10 injections using a treat-and-extend regimen in the first year. The overall mean change in best-corrected visual acuity (BCVA) at one year was +8.8 letters in the monthly injection group. Compared to the monthly injection, there was moderate-certainty evidence that the mean difference (MD) in BCVA change at one year for the standard PRN subgroup was -1.7 letters (95% confidence interval (CI) -2.8 to -0.6; 4 trials, 2299 participants), favoring monthly injections. There was low-certainty evidence of a similar BCVA change with the treat-and-extend subgroup (0.5 letters, 95% CI -3.1 to 4.2; 3 trials, 1226 participants). Compared to monthly injection, there was low-certainty evidence that fewer participants gained 15 or more lines of vision with standard PRN treatment at one year (risk ratio (RR) 0.87, 95% CI 0.76 to 0.99; 4 trials, 2299 participants) and low-certainty evidence of a similar gain with treat-and-extend versus monthly regimens (RR 1.11, 95% CI 0.91 to 1.36; 3 trials, 1169 participants). The mean change in central retinal thickness was a decrease of -166 µm in the monthly injection group; the MD compared with standard PRN was 21 µm (95% CI 6 to 32; 4 trials, 2215 participants; moderate-certainty evidence) and with treat-and extend was 22 µm (95% CI 37 to -81 µm; 2 trials, 635 participants; low-certainty evidence), in favor of monthly injection. Only one trial (498 participants) measured quality of life and reported no evidence of a difference between regimens, but data could not be extracted (low-certainty evidence). Both PRN regimens (standard and 'treat-and-extend') used fewer injections than monthly regimens (standard PRN: MD -4.6 injections, 95% CI -5.4 to -3.8; 4 trials, 2336 participants; treat-and-extend: -2.4 injections, 95% CI -2.7 to -2.1 injections; moderate-certainty evidence for both comparisons). Two trials provided cost data (1105 participants, trials conducted in the US and the UK). They found that cost differences between regimens were reduced if bevacizumab rather than aflibercept or ranibizumab were used, since bevacizumab was less costly (low-certainty evidence). PRN regimens were associated with a reduced risk of endophthalmitis compared with monthly injections (Peto odds ratio (OR) 0.13, 95% CI 0.04 to 0.46; 6 RCTs, 3175 participants; moderate-certainty evidence). Using data from all trials included in this review, we estimated the risk of endophthalmitis with monthly injections to be 8 in every 1000 people per year. The corresponding risk for people receiving PRN regimens was 1 in every 1000 people per year (95% CI 0 to 4). Three trials (1439 participants) compared an extended-fixed regimen (number of injections reported in only one large trial: 7.5 in one year) with monthly injections. There was moderate-certainty evidence that BCVA at one year was similar for extended-fixed and monthly injections (MD in BCVA change compared to extended-fixed group: -1.3 letters, 95% CI -3.9 to 1.3; RR of gaining 15 letters or more: 0.94, 95% CI 0.80 to 1.10). The change in central retinal thickness was a decrease of 137 µm in the monthly group; the MD with the extended-fixed group was 8 µm (95% CI -11 to 27; low-certainty evidence). The frequency of endophthalmitis was lower in the extended-fixed regimen compared to the monthly group, but this estimate was imprecise (RR 0.19, 95% CI 0.03 to 1.11; low-certainty evidence). If we assumed a risk of 8 cases of endophthalmitis in 1000 people receiving monthly injections over one year, then the corresponding risk with extended-fixed regimen was 2 in 1000 people (95% CI 0 to 9). Other evidence comparing different extended-fixed or PRN regimens yielded inconclusive results. AUTHORS' CONCLUSIONS: We found that, at one year, monthly regimens are probably more effective than PRN regimens using seven or eight injections in the first year, but the difference is small and clinically insignificant. Endophthalmitis is probably more common with monthly injections and differences in costs between regimens are higher if aflibercept or ranibizumab are used compared to bevacizumab. This evidence only applies to settings in which regimens are implemented as described in the trials, whereas undertreatment is likely to be common in real-world settings. There are no data from RCTs on long-term effects of different treatment regimens.

How Have Intravitreal Anti-VEGF and Dexamethasone Implant Been Used in Italy? A Multiregional, Population-Based Study in the Years 2010-2016.

PURPOSE: To describe intravitreal anti-VEGF drug and dexamethasone use in four Italian regions. METHODS: Four regional claims databases were used to measure drug prevalence, compare dosing intervals to those recommended in the summary of product characteristics (SPC), and identify switchers. Bilateral treatment and diabetic macular edema (DME) coding algorithms were validated, linking claims with a sample of prospectively collected ophthalmological data. RESULTS: Overall, 41,836 patients received ≥1 study drug in 2010-2016 (4.8 per 10,000 persons). In 2016, anti-VEGF drug use ranged from 0.8 (Basilicata) to 5.7 (Lombardy) per 10,000 persons while intravitreal dexamethasone use ranged from 0.2 (Basilicata) to 1.4 (Lombardy) per 10,000 persons. Overall, 40,815 persons were incident users of study drugs. Among incident users with ≥1 year of follow-up (N = 30,745), 16.0% (N = 30,745), 16.0% (N = 30,745), 16.0% (. CONCLUSION: Study drug use increased over time in Lombardy, Basilicata, Calabria, and Sicily, despite a large heterogeneity in prevalence of use across regions. Drug treatment appeared to be partly in line with SPC, suggesting that improvement in clinical practice may be needed to maximize drug benefits.

Tests for detecting strabismus in children aged 1 to 6 years in the community.

BACKGROUND: Strabismus (misalignment of the eyes) is a risk factor for impaired visual development both of visual acuity and of stereopsis. Detection of strabismus in the community by non-expert examiners may be performed using a number of different index tests that include direct measures of misalignment (corneal or fundus reflex tests), or indirect measures such as stereopsis and visual acuity. The reference test to detect strabismus by trained professionals is the cover‒uncover test. OBJECTIVES: To assess and compare the accuracy of tests, alone or in combination, for detection of strabismus in children aged 1 to 6 years, in a community setting by non-expert screeners or primary care professionals to inform healthcare commissioners setting up childhood screening programmes.Secondary objectives were to investigate sources of heterogeneity of diagnostic accuracy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library, the Health Technology Assessment Database (HTAD) in the Cochrane Library (2016, Issue 4), MEDLINE Ovid (1946 to 5 January 2017), Embase Ovid (1947 to 5 January 2017), CINAHL (January 1937 to 5 January 2017), Web of Science Conference Proceedings Citation Index-Science (CPCI-S) (January 1990 to 5 January 2017), BIOSIS Previews (January 1969 to 5 January 2017), MEDION (to 18 August 2014), the Aggressive Research Intelligence Facility database (ARIF) (to 5 January 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 5 January 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 5 January 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 5 January 2017. We did not use any date or language restrictions in the electronic searches for trials. In addition, orthoptic journals and conference proceedings without electronic listings were searched. SELECTION CRITERIA: All prospective or retrospective population-based test accuracy studies of consecutive participants were included. Studies compared a single or combination of index tests with the reference test. Only those studies with sufficient data for analysis were included specifically to calculate sensitivity and specificity and determine diagnostic accuracy.Participants were aged 1 to 6 years. Studies reporting participants outside this range were included if subgroup data were available.Permitted settings included population-based vision screening programmes or opportunistic screening programmes, such as those performed in schools. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. In brief, two review authors independently assessed titles and abstracts for eligibility and extracted the data, with a third senior author resolving any disagreement. We analysed data primarily for specificity and sensitivity. MAIN RESULTS: One study from a total of 1236 papers, abstracts and trials was eligible for inclusion with a total number of participants of 335 of which 271 completed both the screening test and the gold standard test. The screening test using an automated photoscreener had a sensitivity of 0.46 (95% confidence interval (CI) 0.19 to 0.75) and specificity of 0.97 (CI 0.94 to 0.99). The overall number affected by strabismus was low at 13 (4.8%). AUTHORS' CONCLUSIONS: There is very limited data in the literature to ascertain the accuracy of tests for detecting strabismus in the community as performed by non-expert screeners. A large prospective study to compare methods would be required to determine which tests have the greatest accuracy.

Morphological and Functional Retinal Assessment in Epiretinal Membrane Surgery.

PURPOSE: To analyze functional and morphological findings after surgery for idiopathic epiretinal macular membrane (IEMM). MATERIALS AND METHODS: Twenty eyes of 20 patients affected by IEMM underwent 23-Gauge surgery. Morphological and functional examinations were assessed at baseline and at 30, 90, and 180 days after surgery. SD-OCT evaluated foveal morphology and thickness, photoreceptor inner/outer segment junction, and external limiting membrane. Functional assessment evaluated visual acuity, retinal sensitivity, and fixation patterns. Statistical analysis was performed with the Student's t test and Pearson correlation test. RESULTS: Mean central retinal thickness (CRT), visual acuity (VA), and retinal sensitivity (RS) at baseline were respectively 494.90 ± 38.73 µm, 0.55 ± 0.08 LogMAR, and 11.13±1.02; after surgery, at day 180, we observed a significant decrease in mean CRT to 326.90±32.68 µm, an increase in mean VA to 0.33 ± 0.05 LogMAR (p < 0.05), and in mean RS to 13.25 ± 0.73 dB (p < 0.05). A stable fixation increased from 40% of patients at baseline to 75% of patients at day 180 (p < 0.05). DISCUSSION: IEMM surgery results in continuous improvement in visual function, not only at month one but also beyond month six, due to the progressive reduction of residual intraretinal edema and recomposition of retinal layers.

Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy.

BACKGROUND: Diabetic macular oedema (DMO) is a thickening of the central retina, or the macula, and is associated with long-term visual loss in people with diabetic retinopathy (DR). Clinically significant macular oedema (CSMO) is the most severe form of DMO. Almost 30 years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) found that CSMO, diagnosed by means of stereoscopic fundus photography, leads to moderate visual loss in one of four people within three years. It also showed that grid or focal laser photocoagulation to the macula halves this risk. Recently, intravitreal injection of antiangiogenic drugs has also been used to try to improve vision in people with macular oedema due to DR.Optical coherence tomography (OCT) is based on optical reflectivity and is able to image retinal thickness and structure producing cross-sectional and three-dimensional images of the central retina. It is widely used because it provides objective and quantitative assessment of macular oedema, unlike the subjectivity of fundus biomicroscopic assessment which is routinely used by ophthalmologists instead of photography. Optical coherence tomography is also used for quantitative follow-up of the effects of treatment of CSMO. OBJECTIVES: To determine the diagnostic accuracy of OCT for detecting DMO and CSMO, defined according to ETDRS in 1985, in patients referred to ophthalmologists after DR is detected. In the update of this review we also aimed to assess whether OCT might be considered the new reference standard for detecting DMO. SEARCH METHODS: We searched the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA) and the NHS Economic Evaluation Database (NHSEED) (The Cochrane Library 2013, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2013), EMBASE (January 1950 to June 2013), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to June 2013), BIOSIS Previews (January 1969 to June 2013), MEDION and the Aggressive Research Intelligence Facility database (ARIF). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 25 June 2013. We checked bibliographies of relevant studies for additional references. SELECTION CRITERIA: We selected studies that assessed the diagnostic accuracy of any OCT model for detecting DMO or CSMO in patients with DR who were referred to eye clinics. Diabetic macular oedema and CSMO were diagnosed by means of fundus biomicroscopy by ophthalmologists or stereophotography by ophthalmologists or other trained personnel. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data on study characteristics and measures of accuracy. We assessed data using random-effects hierarchical sROC meta-analysis models. MAIN RESULTS: We included 10 studies (830 participants, 1387 eyes), published between 1998 and 2012. Prevalence of CSMO was 19% to 65% (median 50%) in nine studies with CSMO as the target condition. Study quality was often unclear or at high risk of bias for QUADAS 2 items, specifically regarding study population selection and the exclusion of participants with poor quality images. Applicablity was unclear in all studies since professionals referring patients and results of prior testing were not reported. There was a specific 'unit of analysis' issue because both eyes of the majority of participants were included in the analyses as if they were independent.In nine studies providing data on CSMO (759 participants, 1303 eyes), pooled sensitivity was 0.78 (95% confidence interval (CI) 0.72 to 0.83) and specificity was 0.86 (95% CI 0.76 to 0.93). The median central retinal thickness cut-off we selected for data extraction was 250 µm (range 230 µm to 300 µm). Central CSMO was the target condition in all but two studies and thus our results cannot be applied to non-central CSMO.Data from three studies reporting accuracy for detection of DMO (180 participants, 343 eyes) were not pooled. Sensitivities and specificities were about 0.80 in two studies and were both 1.00 in the third study.Since this review was conceived, the role of OCT has changed and has become a key ingredient of decision-making at all levels of ophthalmic care in this field. Moreover, disagreements between OCT and fundus examination are informative, especially false positives which are referred to as subclinical DMO and are at higher risk of developing clinical CSMO. AUTHORS' CONCLUSIONS: Using retinal thickness thresholds lower than 300 µm and ophthalmologist's fundus assessment as reference standard, central retinal thickness measured with OCT was not sufficiently accurate to diagnose the central type of CSMO in patients with DR referred to retina clinics. However, at least OCT false positives are generally cases of subclinical DMO that cannot be detected clinically but still suffer from increased risk of disease progression. Therefore, the increasing availability of OCT devices, together with their precision and the ability to inform on retinal layer structure, now make OCT widely recognised as the new reference standard for assessment of DMO, even in some screening settings. Thus, this review will not be updated further.

Diffusion-weighted magnetic resonance imaging in the prediction and assessment of chemotherapy outcome in liver metastases.

PURPOSE: This study assessed the capability of magnetic resonance (MR) diffusion-weighted imaging (DwI) with measurement of apparent diffusion coefficient (ADC) in both predicting and evaluating the response to chemotherapy (CHT) of liver metastases by itself and along with preliminary dimensional assessment. METHODS AND MATERIALS: Patients affected by liver metastases from cancers of the digestive tract and breast were prospectively enrolled and underwent computed tomography and MR-DwI before CHT (time 0) and 20-25 days after the beginning of the second cycle (time 3). Moreover, MR-DwI was performed 10-15 (time 1) and 20-25 days (time 2) after the beginning of the first cycle. Maximum diameter and mean ADC value (×10(-3) mm(2)/s) of metastases were evaluated. Lesions were classified as progressive disease (PD), stable disease (SD) or partial response (PR) according to dimensional changes between time 0 and time 3, following RECIST 1.1 indications. Clinically, PD lesions were defined as nonresponding (NR), and SD and PR lesions as responding (R). Analysis of variance and ROC analyses were performed (significance at p < 0.05). RESULTS: Eighty-six metastases (33 patients) were classified as follows: 15 PD, 39 SD and 32 PR without significant differences in mean ADC values among the groups before CHT and at all corresponding times. The mean ADC values of SD and PR groups at times 1 (respectively 1.66 ± 0.36 and 1.59 ± 0.23), 2 (1.72 ± 0.42 and 1.68 ± 0.37) and 3 (1.86 ± 0.44 and 1.73 ± 0.39) were significantly higher than the corresponding values at time 0 (1.50 ± 0.30 and 1.39 ± 0.33). An accurate cutoff value of ADC increase or diameter decrease for the early identification of R or NR lesions was not found. CONCLUSION: The pretreatment ADC value of a liver metastasis does not seem useful in predicting the CHT outcome. A trend towards early ADC increase, alone or occurring with dimensional decrease, may be a good indicator of a responding lesion.

Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for diabetic macular oedema.

BACKGROUND: Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Although grid or focal laser photocoagulation has been shown to reduce the risk of visual loss in DMO or clinically significant macular oedema (CSMO), vision is rarely improved. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) modalities has recently been proposed for improving vision in people with DMO. OBJECTIVES: To assess the effectiveness, safety and cost-effectiveness of anti-VEGF therapy for preserving or improving vision in people with DMO. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to June 2012), EMBASE (January 1980 to June 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2012. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any antiangiogenic drugs with an anti-VEGF mechanism of action versus another treatment, sham treatment, or no treatment in patients with DMO. We also included economic evaluations to assess cost-effectiveness. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data. The risk ratio (RR) of visual loss and visual gain of three or more lines was estimated at least six months after treatment. Each economic analysis was described narratively using a structured format. MAIN RESULTS: Eleven studies provided data on three comparisons of interest in this review. We based our conclusions on the RR of gain or loss of three or more lines of vision at about one year, which was more consistently reported as follow-up.Compared with sham treatment, there was evidence of moderate quality in three studies (497 participants, follow-up 8 to 12 months) that antiangiogenic therapy (pegaptanib: two studies, 246 participants; ranibizumab: one study, 151 participants) doubled and, respectively, halved, the chance of gaining or losing three or more lines of vision (RR: 2.19, 95% confidence interval (CI) 1.36 to 3.53; RR: 0.28, 95% CI: 0.13 to 0.59). In meta-analyses, the benefit was larger for ranibizumab compared to pegaptanib, but no significant subgroup difference could be demonstrated regarding our primary outcome.Compared with grid laser photocoagulation, there was evidence of moderate quality that antiangiogenic therapy (bevacizumab: two studies, 167 participants; ranibizumab: two studies, 300 participants; aflibercept: one study, 221 participants, 89 used for data extraction) more than doubled and, respectively, reduced by at least two thirds, the chance of gaining or losing three or more lines of vision (RR: 3.20, 95% CI 2.07 to 4.95 and RR: 0.13, 95% CI: 0.05 to 0.34, respectively). In meta-analyses, no significant subgroup difference could be demonstrated between bevacizumab, ranibizumab and aflibercept regarding our primary outcome, but, again, there was little power to detect a difference.Compared with grid laser photocoagulation alone, there was high quality evidence that ranibizumab plus photocoagulation (three studies, 783 participants) doubled and, respectively, at least halved, the chance of gaining or losing three or more lines of vision (RR: 2.11, 95% CI 1.67 to 2.67; RR: 0.29, 95% CI: 0.15 to 0.55).Systemic and ocular adverse events were rare in the included studies. Meta-analyses conducted for all antiangiogenic drugs compared with either sham or photocoagulation (nine studies, 104 events in 2159 participants) did not show a significant difference regarding arterial thromboembolic events (RR: 0.85 (0.56 to 1.28). Similarly, no difference was suggested regarding overall mortality (53 events, RR: 0.95 (0.52 to 1.74), but clinically significant differences could not be ruled out. AUTHORS' CONCLUSIONS: There is moderate quality evidence that antiangiogenic drugs provide a definite, but small, benefit compared to current therapeutic options for DMO, i.e. grid laser photocoagulation, or no treatment when laser is not an option. The quality and quantity of the evidence was larger for ranibizumab, but there was little power to investigate drug differences. Most data were obtained at one year, and a long-term confirmation is needed, since DMO is a chronic condition. Safety of both drug and the intravitreal injection procedure were good in the trials, but further long-term data are needed to exclude small, but clinically important differences regarding systemic adverse events.

Reproducibility of fluorescein and indocyanine green angiographic assessment for RAP diagnosis: a multicenter study.

PURPOSE: To explore the interobserver agreement in the diagnosis of retinal angiomatous proliferation (RAP) using fluorescein (FA) and indocyanine green angiographies (ICGA) and to detect which morphologic features of the neovascular lesion are associated with RAP diagnosis. METHODS: In this cross-sectional study, consecutive patients with newly diagnosed neovascular age-related macular degeneration (AMD) evaluated in 8 retina centers were considered. The FA and ICGA were obtained in all centers according to a standard protocol, both performed either as a static or as a dynamic examination. All images were graded by 2 observers from different institutions. RESULTS: A total of 201 eyes with neovascular AMD of 155 consecutive patients (mean age 76±8 years) were considered. Overall RAP prevalence was 30% using FA and 26% using ICGA. Patients studied with dynamic angiography were twice as likely to be diagnosed with RAP as those using static angiography. Interobserver agreement for the overall detection of RAP was high using FA (kappa: 0.868; 95% confidence interval [CI]: 0.793-0.944) and very high using ICGA (kappa: 0.905; 95% CI 0.836-0.974). The agreement between the 2 observers tended to be higher for the truncated vessel than for the anastomosis in FA as well as in ICGA, but no comparison yielded statistical significance (p=0.258 and p=0.584, respectively). CONCLUSIONS: The interobserver agreement for RAP detection was very good both using FA and ICGA, but the overall detection of RAP was higher for dynamic strategy compared with static one.

Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy.

BACKGROUND: Diabetic macular oedema (DMO) is a thickening of the central retina, or the macula, and is associated with long-term visual loss in people with diabetic retinopathy (DR). Clinically significant macular oedema (CSMO) is the most severe form of DMO. Almost 30 years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) found that CSMO, diagnosed by means of stereoscopic fundus photography, leads to moderate visual loss in one of four people within three years. It also showed that grid or focal laser photocoagulation to the macula halves this risk. Recently, intravitreal injection of antiangiogenic drugs has been investigated to try to improve vision in people with macular oedema due to DR.Optical coherence tomography (OCT) is based on optical reflectivity and is able to image retinal thickness and structure producing cross-sectional and three-dimensional images of the central retina. It is already widely used because it provides objective and quantitative assessment of macular oedema unlike the subjectivity of fundus biomicroscopic assessment, which is routinely used by ophthalmologists instead of photography. Optical coherence tomography is also used for quantitative follow up of the effects of treatment of CSMO. Disadvantages of using OCT are the cost to purchase it and the need for trained personnel to perform the examinations. OBJECTIVES: To determine the diagnostic accuracy of OCT for detecting macular oedema in people with DR. A secondary objective is to compare the diagnostic accuracy by study-specific characteristics, such as factors related to methodology, patients or OCT. SEARCH STRATEGY: We searched the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA) and the NHS Economic Evaluation Database (NHSEED) (The Cochrane Library 2011, Issue 5), MEDLINE (January 1950 to May 2011), EMBASE (January 1950 to May 2011), ISI Web of Science (January 1970 to May 2011), BIOSIS Previews (January 1969 to May 2011), MEDION and the Aggressive Research Intelligence Facility database (ARIF). There were no date or language restrictions in the electronic search for trials. The electronic databases were last searched on 16 May 2011. We checked bibliographies of relevant studies for additional references. SELECTION CRITERIA: We selected studies that assessed the diagnostic accuracy of any OCT model for detecting DMO or CSMO in patients with DR who were referred to eye clinics. Diabetic macular oedema and CSMO were diagnosed by means of fundus biomicroscopy by ophthalmologists or stereophotography by ophthalmologists or other trained personnel. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data on study characteristics and measures of accuracy. We assessed data using random-effects hierarchical sROC meta-analysis models. MAIN RESULTS: Nine studies (768 participants, 1325 eyes) were included. Prevalence of CSMO was 19% to 65% (median 50%). Study quality was good for half the QUADAS items, whereas unclear or inadequate quality was found in some studies regarding selection criteria, index and reference test masking (blinding), availability of clinical information, uninterpretable results and withdrawals. There was a specific 'unit of analysis' issue because both eyes of the majority of participants were included in the analyses as if they were independent.Central CSMO was the target condition in all but one study and thus our results cannot be applied to non-central CSMO. In eight studies providing data on CSMO (697 participants, 1241 eyes), pooled sensitivity was 0.78 (95% confidence interval (CI) 0.72 to 0.83) and specificity was 0.86 (95% CI 0.76 to 0.93). The median central retinal thickness cut-off we selected for data extraction was 250 µm (range 230 µm to 300 µm).Data from three studies reporting accuracy for detection of DMO (180 participants, 343 eyes) were not pooled. Sensitivities and specificities were about 0.80 in two studies and were both 1.00 in the third study. AUTHORS' CONCLUSIONS: Central retinal thickness measured with OCT cannot be used as a stand-alone test to diagnose the central type of CSMO and decide on the use of laser photocoagulation in patients who are referred to retina clinics. In fact, there is a substantial disagreement of OCT with the ETDRS definition of CSMO based on clinical examination. Some researchers have observed that OCT can detect macular thickening earlier than clinical examination, but also found that such cases did not necessarily progress to CSMO and need photocoagulation.Care should be taken in applying the conclusions of this review to other test-treatment pathways. In fact, OCT will become an essential tool to manage antiangiogenic therapy, an expanding therapeutic option for patients with macular oedema due to DR, because OCT is a component of the diagnostic algorithms of studies on this new treatment.

Contrast reduction and reading: assessment and reliability with the Reading Explorer test.

PURPOSE: To investigate the reliability of the Reading Explorer (REX) charts and to assess the impact of text contrast reduction (1.5 cycle/degree) on reading speed in subjects with normal and low vision. METHODS: Standard visual acuity (ETDRS charts), reading speed (MNread charts), and contrast sensitivity (Pelli-Robson charts) measurements were obtained in 3 groups of subjects stratified by visual acuity level in the better eye from 0.0 to 1.0 logMAR, with intermediate cutoffs at 0.3 and 0.6 logMAR. Measurements of reading speed for decreasing levels of text contrast were obtained with the REX charts using a 1.5 cycle/degree text. RESULTS: Since in many patients with lower vision a plateau of maximum reading speed across different levels of text contrast was not found, reliability indexes were computed for average reading speed and reading contrast threshold. In the group with lower visual acuity, 95% limits of agreement were +/-0.134 log word/minute and +/-0.175 log contrast sensitivity, suggesting good reliability. The proportion of subjects with a 20% loss of reading speed from 90% to 45% text contrast was estimated to be 1/3 at 0.6 logMAR visual acuity level and 2/3 at 1.0 logMAR. CONCLUSIONS: The adverse effect of decreased text contrast, which may be found in ordinary reading material, on the reading performance of subjects with advanced and initial low vision is probably underestimated. The REX test proved to be a reliable investigation tool for this phenomenon.