Diabetic retinal disease is envisioned to become the plague of the coming decades with a steep increase of worldwide diabetes incidence followed by a substantial rise in retinal disease. Improvements in diagnostic and therapeutic care have to cope with this dilemma in a clinically and socioeconomically efficient manner. Laser treatment has found a less destructive competitor in pharmacological treatments. As a consequence of recent rigorous clinical trials, laser photocoagulation is no longer recommended for the treatment of diabetic macular edema (DME), and anti-vascular endothelial growth factor therapy has emerged as first-line therapy. Steroids have maintained a role in the management of chronically persistent DME. The paradigm shifts in therapy are accompanied by a substantial break-through in diagnostics. The following guidance for the management of DME has been composed from the best updated knowledge of leading experts in Europe and represents another volume in the series of EURETINA recommendations for the management of retinal disease.

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Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA).

Importance Biomarkers that predict future visual acuity (VA) in eyes with baseline diabetic macular edema (DME) would substantively improve risk assessment, management decisions, and selection of eyes for clinical studies targeting DME. Objective To determine whether baseline or early change in the novel spectral domain–optical coherence tomography (SD-OCT) parameter disorganization of the retinal inner layers (DRIL) is predictive of VA in eyes with center-involved DME. Design, Setting, and Participants At a tertiary care referral center for diabetic eye disease, a retrospective, longitudinal cohort study obtained demographics, VA, and SD-OCT images from baseline, 4-month, and 8-month visits in 96 participants (120 eyes) with diabetes mellitus and baseline center-involved DME (SD-OCT central subfield thickness, ≥320 µm for men and ≥305 µm for women). Exclusion criteria included substantial media opacity, cataract surgery within 6 months, and nondiabetic retinal pathology affecting VA. On SD-OCT, the 1-mm-wide retinal area centered on the fovea was evaluated by masked graders for DRIL extent, cysts, hyperreflective foci, microaneurysms, cone outer segment tip visibility, and external limiting membrane or photoreceptor disruption and reflectivity. Main Outcomes and Measures Visual acuity and SD-OCT–derived retinal morphology. Results Greater DRIL extent at baseline correlated with worse baseline VA (point estimate, 0.04; 95% CI, 0.02-0.05 per 100 µm; P P r  = 0.80). Each approximately 300-µm DRIL increase during 4 months predicted a 1-line, 8-month VA decline. When DRIL increased at least 250 µm at 4 months, no eyes had VA improvement of at least 1 line at 8 months. When DRIL decreased at least 250 µm at 4 months, no eyes had VA decline of at least 1 line at 8 months, and 77.7% had VA improvement of at least 1 line. Conclusions and Relevance Disorganization of the retinal inner layers in the 1-mm foveal area is associated with VA, and change in DRIL predicts future change in VA. Early change in DRIL prospectively identifies eyes with a high likelihood of subsequent VA improvement or decline. Therefore, DRIL warrants further study as a robust, readily obtained, and noninvasive biomarker of future VA response in eyes with DME.

https://jamanetwork.com/journals/jamaophthalmology/articlepdf/1889673/eoi140067.pdf

Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema.

A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration.

Despite treatment advances, diabetic eye disease remains a leading cause of visual acuity (VA) loss worldwide. No methods to prospectively determine which patients will gain or lose vision exist, limiting individualized risk assessment and management. We investigated whether noninvasive, readily obtainable spectral domain optical coherence tomography parameters were correlated with VA in eyes with current or resolved center-involved diabetic macular edema (DME). Images were evaluated for disorganization of the retinal inner layers (DRIL), cysts, epiretinal membranes, microaneurysms, subretinal fluid, and outer layer disruption/reflectivity. DRIL affecting ≥50% of the 1-mm central retinal zone was associated with worse VA in all eyes, eyes with current edema, and eyes with resolved edema. Furthermore, early 4-month change in DRIL extent predicted VA change from baseline to 1 year. These data suggest that DRIL is a robust predictor of VA in eyes with present or previous DME and more highly correlated with VA than other widely used measures, such as retinal thickness. If further studies confirm DRIL as a predictive biomarker of future VA, physicians would gain a new tool of substantial clinical and investigative importance that could significantly change the approach to ophthalmic counseling and therapeutic management in patients with diabetes.

https://diabetes.diabetesjournals.org/content/diabetes/64/7/2560.full.pdf

Neural Retinal Disorganization as a Robust Marker of Visual Acuity in Current and Resolved Diabetic Macular Edema

Cystoid macular edema (CME) is observed in a variety of ocular disorders and is strongly associated with vision loss. Optical coherence tomography (OCT) provides excellent visualization of cystoid fluid, and can assist clinicians in monitoring the progression of CME. Quantitative tools for assessing CME may lead to better metrics for choosing treatment protocols. To address this need, this paper presents a fully automated retinal cyst segmentation technique for OCT image stacks acquired from a commercial scanner. The proposed method includes a computationally fast bilateral filter for speckle denoising while maintaining CME boundaries. The proposed technique was evaluated in images from 16 patients with vitreoretinal disease and three controls. The average sensitivity and specificity for the classification of cystoid regions in CME patients were found to be 91% and 96%, respectively, and the retinal volume occupied by cystoid fluid obtained by the algorithm was found to be accurate within a mean and median volume fraction of 1.9% and 0.8%, respectively.

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Automated Segmentation of Intraretinal Cystoid Fluid in Optical Coherence Tomography

Purpose. To determine whether the volume of retinal tissue passing between the inner and outer retina in macular edema could be used as an indicator of visual acuity.

Methods. Diabetic and uveitic patients with cystoid macular edema (81 subjects, 129 eyes) were recruited. Best corrected logMAR visual acuity and spectral optical coherence tomography (OCT/SLO; OTI, Toronto, ONT, Canada) were performed in all patients. Coronal OCT scans obtained from a cross section of the retina between the plexiform layers were analyzed with a grid of five concentric radii (500, 1000, 1500, 2000, and 2500 μm centered on the fovea). The images were analyzed to determine the amount of retinal tissue present within each ring. A linear regression model was developed to determine the relationship between tissue integrity and logMAR visual acuity.

Results. A linear relationship between tissue integrity and VA was demonstrated. The volume of retinal tissue between the plexiform layers in rings 1 and 2 (up to 1000 μm from the foveal center) predicted 80% of visual acuity. By contrast, central macular thickness within the central 1000 μm predicted only 14% of visual acuity.

Conclusions. This study showed that the cross-sectional area of retinal tissue between the plexiform layers in cystoid macular edema, as imaged by OCT, is the best indicator of visual function at baseline. Further prospective treatment trials are needed to investigate this parameter as a predictor of visual outcome after intervention.

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Optical Coherence Tomography May Be Used to Predict Visual Acuity in Patients with Macular Edema

Aim The antibacterial effect of topical anesthetics may lead to false-negative cultures from corneal specimens of bacterial keratitis. This in vitro study compared the antibacterial effect of 3 unpreserved topical anesthetics to indicate the most appropriate agent for corneal scrapes. Methods Four bacterial strains (Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae) derived from the most frequently isolated microorganisms from corneal ulcers were cultured from stored control stocks and clinical specimens. These strains were used to determine the minimum inhibitory concentration (MIC) of 3 preservative-free anesthetic eyedrops: proxymetacaine 0.5%, oxybuprocaine 0.4%, and tetracaine 1%. Results There was no inhibition of growth seen with proxymetacaine 0.5% (5000 microg/mL) with any of the organisms except S. epidermidis, which demonstrated an MIC of 2500 microg/mL (equivalent to a dilution of (1/2)). Tetracaine 1% (10,000 microg/mL) produced an MIC ranging between 625 and 1250 microg/mL, inhibiting all 4 strains at the commercially available dilution. Oxybuprocaine 0.4% (4000 microg/mL) resulted to be the second most inhibitory preparation with an MIC ranging between 1000 and 2000 microg/mL. Conclusions Currently used preservative-free topical anesthetics differ in bacterial growth inhibition. This in vitro study showed that proxymetacaine 0.5% is the least inhibitory on bacterial growth and therefore the most appropriate to be used before corneal scrapes.

Antibacterial activity of preservative-free topical anesthetic drops in current use in ophthalmology departments.

A diagnostic method is disclosed wherein the potential preserved visual acuity in the retina of a patient is determined from the amount of tissue connecting the inner and outer plexiform layers remaining in the retina.

Diagnostic method and apparatus for predicting potential preserved visual acuity

We thank Jay Chhablani and William Freeman for their interest and comments regarding our study. The study validated axonal integrity as a measure of visual potential. In macular edema, abnormal fluid accumulation between the two plexiform layers produces mechanical stress on the bipolar axons. Considering that bipolar axons represent the sole communication between photoreceptors and ganglion cells, any loss of transmission between these neurons significantly compromises visual function. In their letter, Chhablani and Freeman suggest a lack of analysis of other predictors of visual acuity such as macular volume, outer retinal integrity, and IS/OS junction integrity. First, they refer to the integrity of transduction elements rather than transmission elements, the object of our study. These are two completely different entities and therefore are not suitable for a head-to-head comparison. Second, the integrity of transduction elements—photoreceptors and inner segment/outer segment junction (IS/OS junction)—may give a falsely reassuring result, as the photoreceptors may still be intact when the transmission elements, the bipolar axons, have already been permanently damaged. Figure 3B is an example of multiple anatomic abnormalities contributing to visual impairment in macular edema. As far as macular volume is concerned, it is a nonspecific parameter that does not add information as to the role of any anatomic components. The main purpose of this study was to identify and quantify an anatomic predictor of visual potential. By contrast, we compared axonal integrity to OCT-measured central macular thickness, as these two parameters involve the same anatomic elements and are both measurable along the z-axis of the retina. Furthermore, Chhablani and Freeman expressed their concern about the high predictive value generated by retinal axonal integrity versus visual acuity. In fact, anatomically, this is explained by the concepts of convergence and redundancy in retinal architecture. Clinically this is confirmed by the observation that isolated outer retinal structural damage will not produce a directly proportional functional impairment, whereas the loss of axonal integrity may have a more direct impact on visual function. The major strengths of our study are its prospective, objective, quantitative approach and the evaluation of the whole fovea using coronal OCT scans with automated image processing. Unfortunately, the literature on IS/OS junction and external limiting membrane (ELM) integrity is mostly based on retrospective studies describing qualitative parameters on OCT B scans graded by trained observers. Finally, we agree that multifactorial analysis represents the future strategy for the assessment of functional potential in macular diseases and that improved photoreceptor cell function subsequent to drainage of fluid may well increase transduction and therefore have some effect on vision. Lucia Pelosini Christopher C. Hull James F. Boyce Dominic McHugh Miles R. Stanford John Marshall

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Lucia Pelosini

Papers

Optical Coherence Tomography May Be Used to Predict Visual Acuity in Patients with Macular Edema

Antibacterial activity of preservative-free topical anesthetic drops in current use in ophthalmology departments.

Diagnostic method and apparatus for predicting potential preserved visual acuity

Author response: predictors of visual acuity in macular edema.

The Assessment of Optical Coherence Tomography (OCT) as a Predictor of Visual Acuity in Diabetic Macular Oedema