Effect of basic fibroblast growth factor and cytochrome c peroxidase combination in transgenic mice corneal epithelial healing process after excimer laser photoablation

Purpose: To evaluate the role of prepared basic fibroblast growth factor (bFGF) and cytochrome c peroxidase (CCP) combination eyedrops in corneal epithelial healing of transgenic mice (B6(A)-Rperd12/J ) after excimer laser photoablation. Materials and methods: In this prospective study, 216 eyes of 108 mice underwent bilateral photorefractive keratectomy. We considered 4 groups: A, B, C, and D. Group A received standard topical postoperative therapy with tobramycin, diclofenac, and dexamethasone eyedrops plus CCP at 3 drops per day for a week or until corneal re-epithelialization was achieved. Group B received standard topical postoperative therapy plus bFGF eyedrops and phosphate-buffered saline (PBS) 3 drops per day for a week or until corneal re-epithelialization was complete. In group C, 1 eye received standard topical postoperative therapy plus CCP eyedrops, bFGF eyedrops, and PBS 3 drops per day for a week or until corneal re-epithelialization was complete. Control eyes (group D) received a standard topical postoperative therapy plus placebo eyedrops. Mice were followed-up for a week from the day after the surgery to evaluate the rate of corneal re-epithelialization. Results: Data were analyzed by ANOVA using the XLSTAT 2010 software. Eyes in group A, B, and C healed completely before the fifth postoperative day, achieving, respectively, a re-epithelialization time of 92 hours ± 10 SD, 90 hours ± 12 SD, and 86 hours ± 12 SD. Group D had a re-epithelialization time of 121 hours ± 8 SD (P < 0.05). No side effects or toxic effects were documented

OCT Signs of Early Atrophy in Age-Related Macular Degeneration: Interreader Agreement: Classification of Atrophy Meetings Report 6.

PURPOSE: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD). DESIGN: Interreader agreement study. PARTICIPANTS: Twelve readers from 6 reading centers. METHODS: After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy. MAIN OUTCOME MEASURES: Interreader agreement based on Gwet's first-order agreement coefficient (AC1) for qualitatively graded OCT features and classification of iRORA and cRORA, and smallest real difference (SRD) for quantitatively graded OCT features. RESULTS: Substantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (AC1 = 0.63-0.87), except for RPE attenuation (AC1 = 0.46) and disruption (AC1 = 0.26). The lowest SRD for the quantitatively graded horizontal features was observed for the zone of choroidal hypertransmission (± 190.8 μm). Moderate agreement was found for a 3-category classification of no atrophy, iRORA, and cRORA (AC1 = 0.53). Exploratory analyses suggested a significantly higher level of agreement for a 3-category classification using (1) no atrophy; (2) presence of inner nuclear layer and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band, as a less severe atrophic grade; and (3) the latter plus an additional requirement of choroidal hypertransmission of 250 μm or more for a more severe atrophic grade (AC1 = 0.68; P = 0.013). CONCLUSIONS: Assessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement

Optical Coherence Tomography Angiography of the Choriocapillaris in Age-Related Macular Degeneration

The advent of optical coherence tomography angiography (OCTA) has allowed for remarkable advancements in our understanding of the role of the choriocapillaris in age-related macular degeneration (AMD). As a relatively new imaging modality, techniques to analyze and quantify choriocapillaris images are still evolving. Quantification of the choriocapillaris requires careful consideration of many factors, including the type of OCTA device, segmentation of the choriocapillaris slab, image processing techniques, and thresholding method. OCTA imaging shows that the choriocapillaris is impaired in intermediate non-neovascular AMD, and the severity of impairment may predict the advancement of disease. In advanced atrophic AMD, the choriocapillaris is severely impaired underneath the area of geographic atrophy, and the level of impairment surrounding the lesion predicts the rate of atrophy enlargement. Macular neovascularization can be readily identified and classified using OCTA, but it is still unclear if neovascularization features with OCTA can predict the lesion’s level of activity. The choriocapillaris surrounding macular neovascularization is impaired while the more peripheral choriocapillaris is spared, implying that choriocapillaris disruption may drive neovascularization growth. With continued innovation in OCTA image acquisition and analysis methods, advancement in clinical applications and pathophysiologic discoveries in AMD are set to follow

Optic disc pit associated with an unusual outer retinal hole and nasal peripheral retinoschisis

PURPOSE To document a peculiar case of optic disc pit-associated maculopathy (ODP-M) with extensive nasal retinoschisis with lamellar outer retinal hole. METHODS Case report. PATIENT A 41 year-old woman presented to the eye clinic complaining of new photopsias and enlargement of the blind spot in the left eye. Uncorrected visual acuity was 20/20 in both eyes. Fundus examination of the left eye revealed an anomalous appearing optic nerve with a gray oval depression at the temporal margin of the disk consistent with an ODP. RESULTS Optical coherence tomography confirmed the presence of the pit and demonstrated outer plexiform layer schisis superonasal to the fovea as well as extensive inner and outer retinal schisis nasal to the nerve extending to the equator. A large lamellar outer retinal hole was noted nasal to the disk without associated retinal detachment. The vitreous appeared to be attached over the nasal retina. DISCUSSION Multimodal imaging revealed an unusual ODP associated retinopathy with dramatically more extensive retinoschisis and a lamellar outer retinal hole nasal to the nerve despite the temporal location of the pit. Although the precise pathophysiologic mechanisms are not fully understood, forces associated with the vitreo-retinal adhesion may have contributed to the distribution of the schisis in this case

Advances in Optical Coherence Tomography Imaging Technology and Techniques for Choroidal and Retinal Disorders

Optical coherence tomography (OCT) imaging has played a pivotal role in the field of retina. This light-based, non-invasive imaging modality provides high-quality, cross-sectional analysis of the retina and has revolutionized the diagnosis and management of retinal and choroidal diseases. Since its introduction in the early 1990s, OCT technology has continued to advance to provide quicker acquisition times and higher resolution. In this manuscript, we discuss some of the most recent advances in OCT technology and techniques for choroidal and retinal diseases. The emerging innovations discussed include wide-field OCT, adaptive optics OCT, polarization sensitive OCT, full-field OCT, hand-held OCT, intraoperative OCT, at-home OCT, and more. The applications of these rising OCT systems and techniques will allow for a closer monitoring of chorioretinal diseases and treatment response, more robust analysis in basic science research, and further insights into surgical management. In addition, these innovations to optimize visualization of the choroid and retina offer a promising future for advancing our understanding of the pathophysiology of chorioretinal diseases

New trends in visual rehabilitation with MP-1 microperimeter biofeedback: optic neural dysfunction

The aim of this study was to evaluate the efficacy of visual rehabilitation with MP-1 microperimeter biofeedback in advanced optic neural dysfunction due to glaucoma, and to precisely characterize fixation stability and location in affected patients. Ten patients (18 eyes) with advanced glaucoma were submitted to a rehabilitation protocol that consisted of: a 25-item questionnaire (National Eye Institute Visual Functioning Que stionnaire); measurement of visual acuity; a reading speed test; microperimetry with fixation study, retinal sensitivity and the bivariate contour ellipse area (BCEA). The rehabilitation program consisted of 10 training sessions of 10 minutes per eye performed over a period of one week and was repeated at four months, eight months, and one year. Statistical analysis was performed using the Student’s t-test and Spearman correlation; p values less than 0.05 were considered statistically significant. In 13 eyes fixation changed from unstable to relatively unstable while its location changed from predominantly eccentric to predominantly central. In five eyes, fixation changed from relatively unstable to stable with a change of location from poor central fixation to predominantly central fixation. Mean retinal sensitivity changed from 7.43±8.28 dB to 8.33±9.04 dB (p0.05); reading speed improved from a mean value of 31.4±4.3 words/minute to 55.6±3.2 words/minute at the end of the training (p<0.05). The BCEA changed from 0.94±0.39 deg2 to 0.86±0.46 deg2 (p=0.76). Rehabilitation with MP-1 biofeedback in patients with advanced glaucoma is a useful means of improving these patients’ fixation stability, reading speed and quality of life

Characterisation of the vascular anterior surface of type 1 macular neovascularisation after anti-VEGF therapy

Background To evaluate whether the status of vasculature at the top of type 1 macular neovascularisation (MNV) could function as mediator of the observed protective effect against the development of complete retinal pigment epithelial and outer retinal atrophy (cRORA). Methods In consecutive treatment-naive patients, the vasculature at the anterior surface of the MNV was isolated using a slab designed to extract the most superficial vascular portion of the MNV lesion showing a choriocapillaris (CC)-like structure which we termed the 'neo-CC'. The ratio between the neo-CC area (isolated using this custom slab) and the MNV area (isolated using the standard outer retina-CC slab) at baseline and at last follow-up was evaluated. Results Forty-four eyes from 44 patients were included. 20 showed cRORA by the final follow-up (median 23 months), whereas 24 did not progress to atrophy (median 23.5 months). The proportion of MNV with neo-CC at the anterior surface was significantly lower in eyes which progressed to cRORA compared with those which did not. The multivariate regression showed that a lower proportion of neo-CC coverage over the MNV was associated with an increased odds for cRORA development. Conclusions More extensive coverage of neo-CC is associated with a lower likelihood of development of macular atrophy in eyes receiving antivascular endothelial growth factor therapy, suggesting the protective effect of a type 1 MNV may be mediated by the development of a neo-CC and may provide insights into the biological significance of MNV as a response mechanism in eyes with age-related macular degeneration

Automated large-scale prediction of exudative AMD progression using machine-read OCT biomarkers.

Age-related Macular Degeneration (AMD) is a major cause of irreversible vision loss in individuals over 55 years old in the United States. One of the late-stage manifestations of AMD, and a major cause of vision loss, is the development of exudative macular neovascularization (MNV). Optical Coherence Tomography (OCT) is the gold standard to identify fluid at different levels within the retina. The presence of fluid is considered the hallmark to define the presence of disease activity. Anti-vascular growth factor (anti-VEGF) injections can be used to treat exudative MNV. However, given the limitations of anti-VEGF treatment, as burdensome need for frequent visits and repeated injections to sustain efficacy, limited durability of the treatment, poor or no response, there is a great interest in detecting early biomarkers associated with a higher risk for AMD progression to exudative forms in order to optimize the design of early intervention clinical trials. The annotation of structural biomarkers on optical coherence tomography (OCT) B-scans is a laborious, complex and time-consuming process, and discrepancies between human graders can introduce variability into this assessment. To address this issue, a deep-learning model (SLIVER-net) was proposed, which could identify AMD biomarkers on structural OCT volumes with high precision and without human supervision. However, the validation was performed on a small dataset, and the true predictive power of these detected biomarkers in the context of a large cohort has not been evaluated. In this retrospective cohort study, we perform the largest-scale validation of these biomarkers to date. We also assess how these features combined with other EHR data (demographics, comorbidities, etc) affect and/or improve the prediction performance relative to known factors. Our hypothesis is that these biomarkers can be identified by a machine learning algorithm without human supervision, in a way that they preserve their predictive nature. The way we test this hypothesis is by building several machine learning models utilizing these machine-read biomarkers and assessing their added predictive power. We found that not only can we show that the machine-read OCT B-scan biomarkers are predictive of AMD progression, we also observe that our proposed combined OCT and EHR data-based algorithm outperforms the state-of-the-art solution in clinically relevant metrics and provides actionable information which has the potential to improve patient care. In addition, it provides a framework for automated large-scale processing of OCT volumes, making it possible to analyze vast archives without human supervision