Oliver Comyn

Diabetic retinopathy: pathogenesis, clinical grading, management and future developments.

Decades of research into the pathophysiology and management of diabetic retinopathy have revolutionized our understanding of the disease process. Diabetic retinopathy is now more accurately defined as a neurovascular rather than a microvascular disease as neurodegenerative disease precedes and coexists with microvascular changes. However, the complexities of the pathways involved in different stages of disease severity continue to remain a challenging issue for drug discovery. Currently, laser photocoagulation is the mainstay of treatment for proliferative diabetic retinopathy, but is gradually being superseded for diabetic macular oedema. However, it is destructive and at best results in a gradual but modest improvement in vision in the long term. So, diabetic retinopathy remains the most prevalent cause of visual impairment in the working‐age population despite established screening programmes, early diagnosis and treatment of the condition. The recent discovery of inhibitors of vascular endothelial growth factor is revolutionizing the management of diabetic retinopathy, particularly diabetic macular oedema. However, not all patients respond to anti‐vascular endothelial growth factor agents, reinforcing the fact that diabetic retinopathy is a multifactorial disease. Studies are still required to improve our understanding of how retinal structure correlates with visual function. It is hoped that these will lead to better characterization of the disease phenotype based on treatment responses to different agents and allow an algorithm to be developed that will guide the management of diabetic retinopathy and diabetic macular oedema at different stages of severity.

Plusoptix Vision Screener™: The accuracy and repeatability of refractive measurements using a new autorefractor

Background: The Plusoptix Vision Screener (PVS) is a new non-cycloplegic videoretinoscopy autorefractor. Refractive accuracy may affect its performance as a screening tool. Aims: Study 1: To determine the intra- and interobserver variability of PVS measurements. Study 2: To compare PVS measurements with gold-standard manual cycloplegic retinoscopy (MCR). Methods: Study 1: PVS refraction of 103 children with mean (SD) age 5.5 (0.6) years by two observers. Study 2: PVS and MCR refraction of 126 children with mean (SD) age 5.5 (1.5) years, including 43 children with manifest strabismus ⩾5 PD, comparing mean spherical equivalent (MSE) and Jackson cross cylinders J0 and J45. Results: Study 1: Repeatability coefficients (observer 1): MSE: 0.63 D, J0: 0.24 D, J45: 0.18 D; those of observer 2 were nearly identical. The mean difference (95% limits of agreement) between the two observers for MSE, J0 and J45 were, respectively, 0.03 (−0.62 to 0.68 D), −0.008 (−0.25 to 0.23 D) and 0.013 (−0.18 to 0.20) D. Study 2: MSE tended to be lower on PVS than MCR, with differences of up to 8.00 D. Less than 20% of values were within ±0.50 D of each other. Agreement was better for J0 and J45. Strabismus was associated with an odds ratio of 3.7 (95% CI 1.3 to 10.5) of the PVS failing to obtain a reading. Conclusions: The PVS may underestimate children’s refractive error.

The Effect of Multispot Laser Panretinal Photocoagulation on Retinal Sensitivity and Driving Eligibility in Patients With Diabetic Retinopathy

IMPORTANCE Panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR) may lead to peripheral field loss that prevents driving. Anti-vascular endothelial growth factor agents are proposed as treatments for PDR that spare peripheral vision. If multispot lasers cause less visual field loss, continuing to perform PRP may be justified. OBJECTIVE To assess the effect of bilateral multispot laser PRP on retinal sensitivity and driving visual fields in PDR. DESIGN, SETTING, AND PARTICIPANTS This prospective nonrandomized interventional cohort analysis performed at a tertiary referral center included 43 laser-naive patients with PDR that required bilateral PRP. Participants were recruited from June 27, 2012, to October 14, 2013. At baseline and 6-month follow-up, patients underwent detailed static and kinetic perimetry, microperimetry, optical coherence tomography, wide-field color fundus photography, and fluorescein angiography. Quantitative change in retinal sensitivity was assessed by comparing the mean global retinal sensitivity before and after laser treatment and by comparing the modeled hill of vision by deriving a volumetric measure. Final follow-up was completed on May 21, 2014. INTERVENTIONS Multispot laser treatment was applied using standard parameters, until neovascularization regressed or complete retinal coverage was achieved. MAIN OUTCOMES AND MEASURES Participants who passed the Esterman binocular visual field test for driving in the United Kingdom (at least 120° horizontal field with no significant defects within the central 20°) and full-field and macular retinal sensitivity. RESULTS Of the 43 patients (17 men; 26 women; mean [SD] age, 46.6 [13.3] years), 38 (88%) completed the study. Before treatment, 41 of 43 patients (95%) passed the Esterman visual field test for driving; after completion of laser treatment, 35 of 38 patients (92%) passed. The mean (SD) change in retinal sensitivity on static perimetry was -1.4 (3.7) (95% CI, -2.7 to -0.1) dB OD and -2.4 (2.9) (95% CI, -3.4 to -1.4) dB OS. Mean (SD) 4° macular sensitivity decreased by 3.0 (5.2) dB OD and 2.6 (5.4) dB OS. CONCLUSIONS AND RELEVANCE This prospective study investigating the effects of multispot laser PRP on retinal sensitivity demonstrates a high likelihood of retaining eligibility to drive based on adequate visual field. A mild loss of retinal sensitivity was detected at 6 months after completion of laser treatment. Further change to visual fields may have occurred with longer follow-up. This study provides information that might be used to counsel patients requiring PRP and informs the debate regarding the role of anti-vascular endothelial growth factor therapy in patients with PDR who might otherwise receive laser treatment.

Diagnostic accuracy of disorganization of the retinal inner layers in detecting macular capillary non-perfusion in diabetic retinopathy.

Disorganization of the retinal inner layers (DRIL) on optical coherence tomography (OCT) is thought to represent retinal capillary non‐perfusion (CNP) in eyes with diabetic retinopathy. This study was designed to evaluate the ability of DRIL to accurately predict CNP.

Corticosteroid intravitreal implants vs. ranibizumab for the treatment of vitreoretinal disease.

Purpose of review Three long-acting corticosteroid implants are now available for the treatment of retinal disease, offering control of macular edema and inflammation for between 6 months and up to 3 years. This review evaluates their efficacy and side-effect profile in comparison with the antivascular endothelial growth factor agent ranibizumab in diabetic macular edema, retinal vein occlusion, pseudophakic macular edema, and uveitis. Recent findings Trials of ranibizumab in diabetic macular edema have demonstrated excellent efficacy without serious safety concerns to date. Fluocinolone acetonide implants can be considered, but have a high risk of cataract and sequelae from intraocular pressure rise. In retinal vein occlusion, both ranibizumab and Ozurdex have been shown to be effective, although their relative efficacy has not been determined in head-to-head clinical trials. In pseudophakic and uveitic macular edema, steroid implants are probably the first choice therapy, although there is evidence that ranibizumab is effective. For choroidal neovascularization secondary to inflammatory disease, ranibizumab is indicated, whereas Retisert has been shown to reduce the risk of uveitis relapse. Summary In diabetic macular edema, ranibizumab has shown greater efficacy with fewer side-effects than steroid implants. Both ranibizumab and steroid implants can be considered in retinal vein occlusion, but trials are awaited to determine their relative efficacy.

Differences in the topographic profiles of retinal thickening in eyes with and without serous macular detachment associated with diabetic macular oedema.

Purpose To investigate if cases of diabetic macular oedema (DMO) associated with serous macular detachment (SMD) have a different topographic profile of retinal thickening compared with DMO cases not associated with SMD. Methods Optical coherence tomography scans of 152 eyes from 152 patients with centre-involving DMO and central subfield thickness >350 µm were identified. Measurements were taken of the neural retina at the highest point of thickening within the central subfield (H) and lateral extent of retina thicker than 350 µm (W). Group means were compared between eyes with SMD and eyes without SMD. Results SMD was present in 55 eyes (36%). H was lower in eyes with SMD than in eyes without SMD (396 µm vs 550 µm, p<0.001) while W was higher in eyes with SMD compared with eyes without SMD (4.74 mm vs 4.18 mm, p=0.011). Conclusions There were distinct differences in topographical profiles of retinal thickening between eyes with SMD and eyes without SMD. These findings suggest a possible mechanical basis for the pathogenesis of SMD in DMO.

Ranibizumab pretreatment in diabetic vitrectomy a pilot randomised controlled trial (the RaDiVit study)

PurposeOur aim was to evaluate the impact of intravitreal ranibizumab pretreatment on the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy. The objective was to determine the feasibility of a subsequent definitive trial and estimate the effect size and variability of the outcome measure.Patients and methodsWe performed a pilot randomised double-masked single-centre clinical trial in 30 participants with tractional retinal detachment associated with proliferative diabetic retinopathy. Seven days prior to vitrectomy surgery, participants were randomly allocated to receive either intravitreal ranibizumab (Lucentis, Novartis Pharmaceuticals UK Ltd, Frimley, UK) or subconjunctival saline (control). The primary outcome was best-corrected visual acuity 12 weeks following surgery.ResultsAt 12 weeks, the mean (SD) visual acuity was 46.7 (25) ETDRS letters in the control group and 52.6 (21) letters in the ranibizumab group. Mean visual acuity improved by 14 (31) letters in the control group and by 24 (27) letters in the ranibizumab group. We found no difference in the progression of tractional retinal detachment prior to surgery, the duration of surgery, or its technical difficulty. Vitreous cavity haemorrhage persisted at 12 weeks in two of the control group but none of the ranibizumab group.ConclusionRanibizumab pretreatment may improve the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy by reducing the extent of post-operative vitreous cavity haemorrhage. However, the effect size appears to be modest; we calculate that a definitive study to establish a minimally important difference of 5.9 letters at a significance level of P<0.05 would require 348 subjects in each arm.

Spectral-domain optical coherence tomography in subjects over 60 years of age, and its implications for designing clinical trials

We read with interest the paper by Caramoy et al recently published in the British Journal of Ophthalmology —our attention having been captured by the inclusion of clinical trial design in its title.1 Developments in stem cell treatments and the advent of anti-vascular endothelial growth factor treatments have very much placed ophthalmic clinical trials in the public arena. We feel however that the main conclusion drawn by the authors that ‘clinical trials using central retinal thickness as an endpoint are feasible in terms of sample size needed’ needs to be tempered in the light of the following issues. 1. Power : Designing a clinical trial with 80% power means that there is a 20% chance of missing …