Canaloplasty in the Treatment of Open-Angle Glaucoma: A Review of Patient Selection and Outcomes.

Canaloplasty is a relatively new non-penetrating surgery for the reduction of intraocular pressure in patients affected by glaucoma. The technique uses a microcatheter to perform a 360 º cannulation of Schlemm's canal and leaves in place a tension suture providing an inward distension. It aims to restore the physiological outflow pathways of the aqueous humour and is independent of external wound healing. Several studies have shown that canaloplasty is effective in reducing intraocular pressure and has a low rate of complications, especially compared with trabeculectomy, the gold standard for glaucoma surgery. Currently, canaloplasty is indicated in patients with open-angle glaucoma, having a mild to moderate disease, and the combination with cataract phacoemulsification may provide further intraocular pressure reduction. This article reviews canaloplasty indications, results and complications and analyses its outcomes compared with traditional penetrating and non-penetrating techniques

Diagnostic accuracy of optical coherence tomography for diagnosing glaucoma: secondary analyses of the GATE study

Background/Aims: To assess the diagnostic performance of retinal nerve fibre layer (RNFL) data of optical coherence tomography (OCT) for detecting glaucoma. Methods: Secondary analyses of a prospective, multicentre diagnostic study (Glaucoma Automated Tests Evaluation (GATE)) referred to hospital eye services in the UK were conducted. We included data from 899 of 966 participants referred to hospital eye services with suspected glaucoma or ocular hypertension. We used both eyes’ data and logistic regression-based receiver operator characteristics analysis to build a set of models to measure the sensitivity and specificity of the average and inferior quadrant RNFL thickness data of OCT. The reference standard was expert clinician examination including automated perimetry. The main outcome measures were sensitivity at 0.95 specificity and specificity at 0.95 sensitivity and the corresponding RNFL thickness thresholds. We explored the possibility of accuracy improvement by adding measures of within-eye and between-eye variation, scan quality, intraocular pressure (IOP) and age. Results: Glaucoma was diagnosed in at least one eye in 17% of participants. Areas under the curve were between 0.83 and 0.88. When specificity was fixed at 0.95, the sensitivity was between 0.38 and 0.55, and the highest values were reached with models including the inferior quadrant rather than the average RNFL thickness. Fixing specificity at 0.95, the sensitivity was between 0.36 and 0.58. The addition of age, refractive error, IOP or within-subject variation did not improve the accuracy. Conclusion: RNFL thickness data of OCT can be used as a diagnostic test, but accuracy estimates remain moderate even in exploratory multivariable modelling of aiming to improve accuracy

Optic nerve head and fibre layer imaging for diagnosing glaucoma

Background The diagnosis of glaucoma is traditionally based on the finding of optic nerve head (ONH) damage assessed subjectively by ophthalmoscopy or photography or by corresponding damage to the visual field assessed by automated perimetry, or both. Diagnostic assessments are usually required when ophthalmologists or primary eye care professionals find elevated intraocular pressure (IOP) or a suspect appearance of the ONH. Imaging tests such as confocal scanning laser ophthalmoscopy (HRT), optical coherence tomography (OCT) and scanning laser polarimetry (SLP, as used by the GDx instrument), provide an objective measure of the structural changes of retinal nerve fibre layer (RNFL) thickness and ONH parameters occurring in glaucoma. Objectives To determine the diagnostic accuracy of HRT, OCT and GDx for diagnosing manifest glaucoma by detecting ONH and RNFL damage. Search methods We searched several databases for this review. The most recent searches were on 19 February 2015. Selection criteria We included prospective and retrospective cohort studies and case-control studies that evaluated the accuracy of OCT, HRT or the GDx for diagnosing glaucoma. We excluded population-based screening studies, since we planned to consider studies on self-referred people or participants in whom a risk factor for glaucoma had already been identified in primary care, such as elevated IOP or a family history of glaucoma. We only considered recent commercial versions of the tests: spectral domain OCT, HRT III and GDx VCC or Data collection and analysis We adopted standard Cochrane methods. We fitted a hierarchical summary ROC (HSROC) model using the METADAS macro in SAS software. After studies were selected, we decided to use 2 x 2 data at 0.95 specificity or closer in meta-analyses, since this was the most commonly-reported level. Main results We included 106 studies in this review, which analysed 16,260 eyes (8353 cases, 7907 controls) in total. Forty studies (5574 participants) assessed GDx, 18 studies (3550 participants) HRT, and 63 (9390 participants) OCT, with 12 of these studies comparing two or three tests. Regarding study quality, a case-control design in 103 studies raised concerns as it can overestimate accuracy and reduce the applicability of the results to daily practice. Twenty-four studies were sponsored by the manufacturer, and in 15 the potential conflict of interest was unclear. Comparisons made within each test were more reliable than those between tests, as they were mostly based on direct comparisons within each study. The Nerve Fibre Indicator yielded the highest accuracy (estimate, 95% confidence interval (CI)) among GDx parameters (sensitivity: 0.67, 0.55 to 0.77; specificity: 0.94, 0.92 to 0.95). For HRT measures, the Vertical Cup/Disc (C/D) ratio (sensitivity: 0.72, 0.60 to 0.68; specificity: 0.94, 0.92 to 0.95) was no different from other parameters. With OCT, the accuracy of average RNFL retinal thickness was similar to the inferior sector (0.72, 0.65 to 0.77; specificity: 0.93, 0.92 to 0.95) and, in different studies, to the vertical C/D ratio. Comparing the parameters with the highest diagnostic odds ratio (DOR) for each device in a single HSROC model, the performance of GDx, HRT and OCT was remarkably similar. At a sensitivity of 0.70 and a high specificity close to 0.95 as in most of these studies, in 1000 people referred by primary eye care, of whom 200 have manifest glaucoma, such as in those who have already undergone some functional or anatomic testing by optometrists, the best measures of GDx, HRT and OCT would miss about 60 cases out of the 200 patients with glaucoma, and would incorrectly refer 50 out of 800 patients without glaucoma. If prevalence were 5%, e.g. such as in people referred only because of family history of glaucoma, the corresponding figures would be 15 patients missed out of 50 with manifest glaucoma, avoiding referral of about 890 out of 950 non-glaucomatous people. Heterogeneity investigations found that sensitivity estimate was higher for studies with more severe glaucoma, expressed as worse average mean deviation (MD): 0.79 (0.74 to 0.83) for MD < -6 db versus 0.64 (0.60 to 0.69) for MD >=-6 db, at a similar summary specificity (0.93, 95% CI 0.92 to 0.94 and, respectively, 0.94; 95% CI 0.93 to 0.95; P < 0.0001 for the difference in relative DOR). Authors' conclusions The accuracy of imaging tests for detecting manifest glaucoma was variable across studies, but overall similar for different devices. Accuracy may have been overestimated due to the case-control design, which is a serious limitation of the current evidence base. We recommend that further diagnostic accuracy studies are carried out on patients selected consecutively at a defined step of the clinical pathway, providing a description of risk factors leading to referral and bearing in mind the consequences of false positives and false negatives in the setting in which the diagnostic question is made. Future research should report accuracy for each threshold of these continuous measures, or publish raw data

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 ofmacular 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 afterDR is detected. In the update of this review we also aimed to assess whetherOCTmight 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 anyOCTmodel for detectingDMOorCSMOin patientswithDR whowere 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 \uce\ubcm (range 230 \uce\ubcm to 300 \uce\ubcm). 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 \uce\ubcm 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

A Simple Subjective Evaluation of Enface OCT Reflectance Images Distinguishes Glaucoma From Healthy Eyes

yesPurpose: We present a subjective approach to detecting glaucomatous defects in enface images and assess its diagnostic performance. We also test the hypothesis that if reflectivity changes precede thickness changes in glaucoma there should be reduced correlation between the modalities in glaucoma compared to controls. Methods: Twenty glaucoma participants and 20 age-matched controls underwent high-resolution OCT scans of one eye. 4 μm-thick enface slabs were constructed through the retina. Enface indices were depths of first gap in visible retinal nerve fiber bundles (RNFBs) and last visible bundle, subjectively evaluated in six sectors of a 3.5 mm circle around the optic disc. Retinal nerve fiber layer thickness (RNFLT) along the same circle was extracted at angles corresponding to enface indices. Between-group differences were tested by linear mixed models. Diagnostic performance was measured by partial receiver operating characteristic area (pAUC). Results: First gap and last visible bundle were closer to the inner limiting membrane in glaucoma eyes (both P < 0.0001). Enface indices showed excellent diagnostic perfor mance (pAUCs 0.63–1.00), similar to RNFLT (pAUCs 0.63–0.95). Correlation between enface and RNFLT parameters was strong in healthy (r = 0.81–0.92) and glaucoma eyes (r = 0.73–0.80). Conclusions: This simple subjective method reliably identifies glaucomatous defects in enface images with diagnostic performance at least as good as existing thickness indices. Thickness and reflectivity were similarly related in healthy and glaucoma eyes, providing no strong evidence of reflectivity loss preceding thinning. Objective analyses may realize further potential of enface OCT images in glaucoma. Translational Relevance: Novel enface OCT indices may aid glaucoma diagnosis

Laser photocoagulation for proliferative diabetic retinopathy.

BACKGROUND: Diabetic retinopathy is a complication of diabetes in which high blood sugar levels damage the blood vessels in the retina. Sometimes new blood vessels grow in the retina, and these can have harmful effects; this is known as proliferative diabetic retinopathy. Laser photocoagulation is an intervention that is commonly used to treat diabetic retinopathy, in which light energy is applied to the retina with the aim of stopping the growth and development of new blood vessels, and thereby preserving vision. OBJECTIVES: To assess the effects of laser photocoagulation for diabetic retinopathy compared to no treatment or deferred treatment. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (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 3 June 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where people (or eyes) with diabetic retinopathy were randomly allocated to laser photocoagulation or no treatment or deferred treatment. We excluded trials of lasers that are no longer in routine use. Our primary outcome was the proportion of people who lost 15 or more letters (3 lines) of best-corrected visual acuity (BCVA) as measured on a logMAR chart at 12 months. We also looked at longer-term follow-up of the primary outcome at two to five years. Secondary outcomes included mean best corrected distance visual acuity, severe visual loss, mean near visual acuity, progression of diabetic retinopathy, quality of life, pain, loss of driving licence, vitreous haemorrhage and retinal detachment. DATA COLLECTION AND ANALYSIS: We used standard methods as expected by the Cochrane Collaboration. Two review authors selected studies and extracted data. MAIN RESULTS: We identified a large number of trials of laser photocoagulation of diabetic retinopathy (n = 83) but only five of these studies were eligible for inclusion in the review, i.e. they compared laser photocoagulation with currently available lasers to no (or deferred) treatment. Three studies were conducted in the USA, one study in the UK and one study in Japan. A total of 4786 people (9503 eyes) were included in these studies. The majority of participants in four of these trials were people with proliferative diabetic retinopathy; one trial recruited mainly people with non-proliferative retinopathy. Four of the studies evaluated panretinal photocoagulation with argon laser and one study investigated selective photocoagulation of non-perfusion areas. Three studies compared laser treatment to no treatment and two studies compared laser treatment to deferred laser treatment. All studies were at risk of performance bias because the treatment and control were different and no study attempted to produce a sham treatment. Three studies were considered to be at risk of attrition bias.At 12 months there was little difference between eyes that received laser photocoagulation and those allocated to no treatment (or deferred treatment), in terms of loss of 15 or more letters of visual acuity (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.89 to 1.11; 8926 eyes; 2 RCTs, low quality evidence). Longer term follow-up did not show a consistent pattern, but one study found a 20% reduction in risk of loss of 15 or more letters of visual acuity at five years with laser treatment. Treatment with laser reduced the risk of severe visual loss by over 50% at 12 months (RR 0.46, 95% CI 0.24 to 0.86; 9276 eyes; 4 RCTs, moderate quality evidence). There was a beneficial effect on progression of diabetic retinopathy with treated eyes experiencing a 50% reduction in risk of progression of diabetic retinopathy (RR 0.49, 95% CI 0.37 to 0.64; 8331 eyes; 4 RCTs, low quality evidence) and a similar reduction in risk of vitreous haemorrhage (RR 0.56, 95% CI 0.37 to 0.85; 224 eyes; 2 RCTs, low quality evidence).None of the studies reported near visual acuity or patient-relevant outcomes such as quality of life, pain, loss of driving licence or adverse effects such as retinal detachment.We did not plan any subgroup analyses, but there was a difference in baseline risk in participants with non-proliferative retinopathy compared to those with proliferative retinopathy. With the small number of included studies we could not do a formal subgroup analysis comparing effect in proliferative and non-proliferative retinopathy. AUTHORS' CONCLUSIONS: This review provides evidence that laser photocoagulation is beneficial in treating proliferative diabetic retinopathy. We judged the evidence to be moderate or low, depending on the outcome. This is partly related to reporting of trials conducted many years ago, after which panretinal photocoagulation has become the mainstay of treatment of proliferative diabetic retinopathy.Future Cochrane Reviews on variations in the laser treatment protocol are planned. Future research on laser photocoagulation should investigate the combination of laser photocoagulation with newer treatments such as anti-vascular endothelial growth factors (anti-VEGFs)