Rui Bernardes

Macular alterations after small-incision cataract surgery

Purpose: To characterize macular edema that occurs after uneventful cataract surgery. Setting: Centre of Ophthalmology, University Hospital, Institute of Biomedical Research on Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Methods: Thirty‐two eyes of 32 patients had uneventful phacoemulsification with implantation of a foldable intraocular lens. Postoperatively, patients were examined at 3, 6, 12, and 30 weeks. The examinations included retinal leakage analysis (Zeiss CSLO), optical coherence tomography (Humphrey Instruments), and retinal thickness analysis (Talia Technology, Ltd.). Results were compared with those in a control group comprising healthy subjects. Results: Increases in retinal thickness (ie, over the mean ± 2 SD in the control group) reached a maximum at 6 weeks in 13 of 32 eyes (41%), after which recovery was progressive. At 30 weeks, all eyes had good visual acuity, but 7 eyes (22%) still had macular edema. The edema was located primarily in the central macular region. Leaking sites involving the vascular areas of the macula, which indicated areas of abnormal blood–retinal barrier permeability, were a frequent finding. The number of sites remained relatively stable during the first 12 weeks (88%) and decreased to 68% at 30 weeks, indicating a trend toward recovery. Conclusion: Macular edema after cataract surgery occurred primarily in the central region of the macula and was associated with the presence of leaking sites, which were located predominantly in the vascular regions of the central macula.

Digital ocular fundus imaging: a review

Ocular fundus imaging plays a key role in monitoring the health status of the human eye. Currently, a large number of imaging modalities allow the assessment and/or quantification of ocular changes from a healthy status. This review focuses on the main digital fundus imaging modality, color fundus photography, with a brief overview of complementary techniques, such as fluorescein angiography. While focusing on two-dimensional color fundus photography, the authors address the evolution from nondigital to digital imaging and its impact on diagnosis. They also compare several studies performed along the transitional path of this technology. Retinal image processing and analysis, automated disease detection and identification of the stage of diabetic retinopathy (DR) are addressed as well. The authors emphasize the problems of image segmentation, focusing on the major landmark structures of the ocular fundus: the vascular network, optic disk and the fovea. Several proposed approaches for the automatic detection of signs of disease onset and progression, such as microaneurysms, are surveyed. A thorough comparison is conducted among different studies with regard to the number of eyes/subjects, imaging modality, fundus camera used, field of view and image resolution to identify the large variation in characteristics from one study to another. Similarly, the main features of the proposed classifications and algorithms for the automatic detection of DR are compared, thereby addressing computer-aided diagnosis and computer-aided detection for use in screening programs.

Improved adaptive complex diffusion despeckling filter

Despeckling optical coherence tomograms from the human retina is a fundamental step to a better diagnosis or as a preprocessing stage for retinal layer segmentation. Both of these applications are particularly important in monitoring the progression of retinal disorders. In this study we propose a new formulation for a well-known nonlinear complex diffusion filter. A regularization factor is now made to be dependent on data, and the process itself is now an adaptive one. Experimental results making use of synthetic data show the good performance of the proposed formulation by achieving better quantitative results and increasing computation speed.

Blood-retinal barrier

The blood-ocular barrier system is formed by 2 main barriers: the blood-aqueous barrier and the blood-retinal barrier (BRB). The BRB is particularly tight and restrictive and is a physiologic barrier that regulates ion, protein, and water flux into and out of the retina. The BRB consists of inner and outer components, the inner BRB being formed of tight junctions between retinal capillary endothelial cells and the outer BRB of tight junctions between retinal pigment epithelial cells. The BRB is essential to maintaining the eye as a privileged site and is essential for normal visual function. Methods of clinical evaluation of the BRB are reviewed and new directions using optical coherence tomography are presented. Alterations of the BRB play a crucial role in the development of retinal diseases. The 2 most frequent and relevant retinal diseases, diabetic retinopathy and age-related macular degeneration (AMD), are directly associated with alterations of the BRB. Diabetic retinopathy is initiated by an alteration of the inner BRB and neovascular AMD is a result of an alteration of the outer BRB. Macular edema is a direct result of alterations of the BRB.

Nonproliferative retinopathy in diabetes type 2. Initial stages and characterization of phenotypes.

This review addresses the initial stages of nonproliferative diabetic retinopathy in diabetes type 2. The natural history of the initial lesions occurring in the diabetic retina has particular relevance for our understanding and management of diabetic retinal disease, one of the major causes of vision loss in the western world. Diabetic retinal lesions are still reversible at this stage opening entirely new opportunities for effective intervention. Four main alterations characterize these early stages of diabetic retinopathy: microaneurysms/hemorrhages, alteration of the blood-retinal barrier, capillary closure and alterations in the neuronal and glial cells of the retina. These alterations may be monitored by red-dot counting on eye fundus images and by fluorescein leakage and retinal thickness measurements. A combination of these methods through multimodal macula mapping has contributed by identifying three different phenotypes of diabetic retinopathy. They show different types and rates of progression which suggest the involvement of different susceptibility genes. The identification of different phenotypes opens the door for genotype characterization, different management strategies targeted treatments.

Microaneurysm Turnover Is a Biomarker for Diabetic Retinopathy Progression to Clinically Significant Macular Edema: Findings for Type 2 Diabetics with Nonproliferative Retinopathy

Purpose: To examine the relationship between microaneurysm turnover (formation rate), using a new semi-automatic method (MA-Tracker) based on color fundus photographs, and diabetic retinopathy (DR) progression to clinically significant macular edema (CSME). Methods: In total, 113 patients/eyes with nonproliferative DR (NPDR) were followed up every 6 months for 2 years as controls of the DR clinical trials, and by conventional general and ophthalmological care for the next 8 years (over a total of 10 years’ follow-up). Microaneurysm turnover for the 2 first years was computed using the MA-Tracker. Results: The 17 patients that developed CSME over the 10 years of follow-up presented a microaneurysm formation rate of 9.2 ± 18.2 microaneurysms/year (mean ± SD) during the first 2 years, which was statistically higher than the eyes that did not develop CSME (0.5 ± 1.2 microaneurysms/year, p < 0.001). These 17 patients also presented higher HbA1C levels at baseline (8.5 ± 1.2%) compared to the patients who did not develop CSME (7.3 ± 1.2%, p = 0.001). Conclusions: A high microaneurysm formation rate on color fundus photographs appears to be a good biomarker for DR progression to CSME in type 2 diabetic patients with NPDR.

Computer-Assisted Microaneurysm Turnover in the Early Stages of Diabetic Retinopathy

Purpose: To assess the reliability of microaneurysm turnover, computed from color fundus photographs, in evaluating diabetic retinopathy in patients with type 2 diabetes and nonproliferative retinopathy. Methods: A new method (MA-Tracker) was developed to count microaneurysms by mapping their locations through image co-registration. To compute the reliability of microaneurysm turnover, 3 different graders were asked to earmark microaneurysms on the same set of color fundus photographs. Results: The total numbers of microaneurysms earmarked in each of 5 visits suggest that microaneurysms remain stable over time (p ≥ 0.138). However, an analysis of each microaneurysm showed that only 29.4% remained at the same location. By computing the formation and disappearance rates of microaneurysms (2.3 and 1.7 microaneurysms/year, respectively), a significant turnover of microaneurysms was found. Conclusions: The formation and disappearance rates of microaneurysms obtained from color fundus photographs using MA-Tracker show very good agreement between different graders, and can be used as indicators of microaneurysm turnover in the initial stages of diabetic retinopathy.

Visual phenotype in Williams-Beuren syndrome challenges magnocellular theories explaining human neurodevelopmental visual cortical disorders

Williams-Beuren syndrome (WBS), a neurodevelopmental genetic disorder whose manifestations include visuospatial impairment, provides a unique model to link genetically determined loss of neural cell populations at different levels of the nervous system with neural circuits and visual behavior. Given that several of the genes deleted in WBS are also involved in eye development and the differentiation of retinal layers, we examined the retinal phenotype in WBS patients and its functional relation to global motion perception. We discovered a low-level visual phenotype characterized by decreased retinal thickness, abnormal optic disk concavity, and impaired visual responses in WBS patients compared with age-matched controls by using electrophysiology, confocal and coherence in vivo imaging with cellular resolution, and psychophysics. These mechanisms of impairment are related to the magnocellular pathway, which is involved in the detection of temporal changes in the visual scene. Low-level magnocellular performance did not predict high-level deficits in the integration of motion and 3D information at higher levels, thereby demonstrating independent mechanisms of dysfunction in WBS that will require remediation strategies different from those used in other visuospatial disorders. These findings challenge neurodevelopmental theories that explain cortical deficits based on low-level magnocellular impairment, such as regarding dyslexia.

Multimodal macula mapping: a new approach to study diseases of the macula.

Multimodal macula mapping is presented as a combination of a variety of diagnostic tools and techniques to examine the macular region in order to obtain information on its structure and function in a clinical environment. Foundations of macular mapping are reviewed and discussed. New methodologies for multimodal macula mapping based on a combination of scanning laser angiography, retinal leakage analysis, retinal thickness analysis, and visual field testing are presented, demonstrating the potential of macula mapping. Other available detection devices are briefly reviewed considering their potential to be included and utilized in future developments of multimodal macula mapping. Multimodal macula mapping appears to offer unique perspectives and insights that are expected to contribute to improved diagnosis and better understanding of macular diseases.

Central retinal thickness measured with HD-OCT shows a weak correlation with visual acuity in eyes with CSME

Aims To investigate the correlation between increased retinal thickness (RT) measured with spectral domain high-definition optical coherence tomography (OCT) (Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, California, USA)) and best-corrected visual acuity (BCVA) in eyes with clinically significant macular oedema (CSME) and type 2 diabetes. Methods Seventy eyes with CSME were included in this observational study. Sixty-two eyes were considered for analysis and were classified as having/not having retinal thickening in the central fovea (central 500-μm-diameter circle) by Cirrus HD-OCT. RT measurements were computed and correlated with BCVA. For comparison purposes, the Stratus OCT (Carl Zeiss Meditec, Dublin, California, USA) central point thickness was also obtained in these eyes. Results In the 19 eyes with CMSE identified by Cirrus HD-OCT without increased RT in the central fovea (500-μm-diameter circle), no correlation was found between RT and BCVA (R=0.062; 95% CI −0.404 to 0.502). In the 43 eyes where the Cirrus HD-OCT identified an increased RT in the central fovea (central 500-μm-diameter circle), only a moderate correlation between RT and BCVA was found (R=−0.459; 95% CI −0.667 to −0.184). Conclusion Correlations between RT and BCVA in CSME are only present when the central 500-μm-diameter circle is involved. However, even in this circumstance, a correlation was found in only 48.8% of the cases. RT cannot, therefore, be used as a surrogate outcome for visual acuity changes.