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PURPOSE: To investigate the plausibility of clinically significant oxygen toxicity in patients with retinal disorders being treated with hyperoxia therapy. Supplemental oxygen therapy is a promising form of treatment that may help reduce ischemia and the subsequent symptoms in patients suffering from diabetic retinopathy (DR), retinal vein occlusions (RVOs), and age-related macular degeneration (AMD). Currently, few studies perform ongoing assessments of current hyperoxia trials in patient populations. By investigating a current cohort of patients using supplemental oxygen to mitigate symptoms in their ocular conditions, we hope to demonstrate the extremely low likelihood of oxygen toxicity in patients utilizing hyperoxia therapy. Through these results, we hope to demonstrate that supplemental oxygen therapy is a viable, safe method of treatment for patients with ocular disorders. METHODS: A cohort of 16 patients was analyzed for changes in their C Reactive Protein (CRP), white blood cell count (WBC), hematocrit (Hct), and hemoglobin (Hb) levels after continuous use of hyperoxia therapy as part of treatment for varying retinal disorders. All study patients were diagnosed and under treatment at Beth Israel Deaconess Medical Center in Boston, MA. Patients diagnosed with diabetic retinopathy, retinal vein occlusions, or age-related macular degeneration were included in the study. Each of these patients must have also been prescribed 5 L/min of nocturnal hyperoxia therapy. Patients with insufficient data either before or after beginning the hyperoxia therapy were excluded. Primary outcome variables were arranged as pre- and post- hyperoxia therapy data points for CRP, WBC, Hb, and Hct. P-values below 0.05 would indicate statistically significant risk of oxygen toxicity in these variables under the current hyperoxia treatment. RESULTS: The mean age of the sample population was 64, with 6 of the 16 patients diagnosed with diabetes (37.5%). Patient groups were divided into diabetic vs. non-diabetic to assess whether or not one group was affected differently by the hyperoxia therapy. Results showed p-values well over 0.05 for both groups, indicating that oxygen toxicity is not a major risk factor when using supplemental oxygen under the study’s conditions. CONCLUSION: A large number of patients with diabetes suffer from retinal problems, especially with the onset of old age. These problems eventually require treatment via eye injections, laser, and even surgery in order to preserve vision and mitigate edema and ischemia. Given the high cost and invasive nature of these procedures, hyperoxia therapy provides a safe and potentially beneficial alternative to mitigate the symptoms of these disorders. This study hoped to demonstrate the plausibility of widespread clinical application for supplemental oxygen therapy in retina patients, while concluding that oxygen toxicity is not a significant risk factor in this type of treatment. The outcomes of this study support this hypothesis, and lay the groundwork for future studies that may assess the risks of oxygen toxicity on a larger scale. More research is required to gauge the true risks of oxygen toxicity in patients using supplemental oxygen. A case-controlled longitudinal study would also prove useful in providing data on changes in visual acuity and other experimental factors of interest, while accounting for several limitations present in this study. / 2021-06-17T00:00:00Z

This research is concerned with the application of neural network techniques to the problems of classifying images in a manner that is invariant to changes in position and scale. In addition to the goal of invariant classification, the network has to classify the objects in a hierarchical manner, in which complex features are constructed from simpler features, and use unsupervised learning. The resultant hierarchical structure should be able to classify the image by having an internal representation that models the structure of the image. After finding existing neural network techniques unsuitable, a new type of neural network was developed that differed from the conventional multi-layer perceptron type of architecture. This network was constructed from neurons that were grouped into feature detectors. These neurons were taught in an unsupervised manner that used a technique based on Kohonen learning. A number of novel techniques were developed to improve the learning and classification performance of the network. The network was able to retain the spatial relationship of the classified features; this inherent property resulted in the capability for position and scale invariant classification. As a consequence, an additional invariance filter was not required. In addition to achieving the invariance property, the developed techniques enabled multiple objects in an image to be classified. When the network had learned the spatial relationships between the lower level features, names could be assigned to the identified features. As part of the classification process, the system was able to identify the positions of the classified features in all layers of the network. A software model of an artificial retina was used to test the grey scale classification performance of the network and to assess the response of the retina to changes in brightness. Like the Neocognitron, the resulting network was developed solely for image classification. Although the Neocognitron is not designed for scale or position invariance, it was chosen for comparison purposes because it has structural similarities and the ability to accommodates light changes in the image. This type of network could be used as the basis for a 2D-scene analysis neural network, in which the inherent parallelism of the neural network would provide simultaneous classification of the objects in the image.

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Idiopathic macular hole is a disease of the eye with unknown cause, but a pathology that, over the course of several decades of investigation by clinicians and researchers alike, has become readily treatable with surgical intervention at a very high rate of successful repair. The current study presents a retrospective case series exploring surgical outcomes for treatment of recurrent macular holes. The study additionally provides a window into the past, present, and future of macular holes across all clinical considerations, and importantly performs a supplementary statistical meta analysis of reoperation success rates in the relevant field of published data- the first of its kind. The introductory background of the present study establishes a natural history of idiopathic macular holes in clinical discovery, classification, and management. The study's case series data specifically focuses on the phenomenon of macular hole recurrence, offering surgical outcome measures of patients undergoing primary and secondary repair operations in a single-center, single-surgeon design. The findings of the retrospective series support the hypothesis that macular hole reoperation does achieve successful anatomical closure in a majority of cases. A meta analysis performed on the current field of published clinical research pertaining to recurrent macular holes established cumulative success rates across a variety of surgical conditions. The present study's findings were then compared to the corresponding measures across the landscape of recurrent macular hole literature, to help inform a niche of clinical research that continues to be an area of investigation and discovery. In presenting a cohesive, synthesized narrative of recurrent macular holes, the study provides a foundation wherein ongoing collaborative efforts in the field can continue to build upon a blueprint currently set in place, and work towards finding a cause behind an otherwise idiopathic disease.

The vertebrate retina, which provides the visual input to the brain and its main interface with the outside world, is a very attractive model system for approaching the question of the information processing role of biological mechanisms of nerve cells. It is as yet impossible to provide a complete circuit diagram of the retina, but it is now possible to identify a few simple computations that the retina performs and to relate them to specific biophysical mechanisms and circuit elements. In this paper we consider three operations carried out by most retinae: amplification, temporal differentiation, and computation of the direction of motion of visual patterns.

During embryonic development, the Hedgehog (Hh) signaling pathway plays an important role in the growth and patterning of numerous tissues and organs. In the developing retina, Hh signaling regulates the proliferation and differentiation of retinal progenitor cells (RPC) through mechanisms that are not completely understood. The principal downstream mediators of the Hh pathway are the Gli transcription factors (Gli1-3), which regulate the expression of target genes responsible for the effects of the Hh pathway on RPC. The network of genes targeted by this pathway in neural progenitor cells however, remains unknown. The objective of this thesis was to identify and characterize novel targets of Hh/Gli during retinal development. Using a computation approach, 390 genes were identified as having at least one conserved Gli binding motif within the vicinity of the coding sequence between humans and mice. During validation, I demonstrate that 30 of 46 selected targets were modulated in response to Hh pathway activation in either E14.5 and/or P0.5 retinal explants and that the induction of 25 of these were significantly different between the two developmental stages. Included in this list of Hh-modulated genes were Sox8 and Ndp, two highly inducible genes that are direct targets of Gli2. Functionally, I was unable to determine a role for Sox8 during retinal development which could reflect compensation by the closely related Sox9 and Sox10 genes. Ndp on the other hand was found to be sufficient and required for Hh mediated induction in progenitor cell proliferation and cell fate determination. Therefore, in this thesis Hh target genes have been identified which could provide some insight into the mechanisms that are responsible for the cellular outcome of a response to the pathway.

Thesis--M. Phil., University of Hong Kong, 1982.

Thesis (M. Phil.)--University of Hong Kong, 1979.

Inhibitor of differentiation (Id) family helix-loop-helix proteins regulate the proliferation, survival and differentiation of numerous cell types during development, however their function during retinal development has not been analyzed. Using loss-of-function and overexpression assays in zebrafish, I demonstrate that Id2a levels modulate retinoblast cell cycle kinetics and thereby influence neuron and glia formation in the retina. Id2a-deficient retinas possess increased numbers of cells occupying S phase, at the expense of mitotic cells, and kinetic analyses demonstrate that Id2a is required for S-phase progression and/or the transition from S to M phase. Id2a-dependent defects in retinoblast proliferation lead to microphthalmia and to an absence of nearly all differentiated inner and outer nuclear layer cell types. Overexpression of id2a has the opposite effect on retinoblast cell cycle kinetics: id2a-overexpressing retinoblasts progress from S to M phase more rapidly and they undergo mitosis more frequently, which results in macrophthalmia. Mosaic analyses reveal that Id2a function in facilitating both cell cycle progression and neuronal differentiation in the retina is non-cell-autonomous, suggesting that Id2a functions upstream of the extrinsic pathways that regulate retinogenesis. In an effort to identify which extrinsic pathways function downstream of Id2a, I discovered that Id2a function is necessary and sufficient to limit Notch pathway activity during retinogenesis. Id2a-deficient retinae possess elevated levels of Notch pathway component gene expression, while retinae overexpressing id2a possess reduced expression of Notch pathway component genes. Attenuation of Notch signaling activity by DAPT or by morpholino knockdown of Notch1a is sufficient to rescue both the proliferative and differentiation defects in Id2a-deficient retinae. In addition to regulating Notch pathway activity, through an RNA-Seq and differential gene expression analysis of Id2a-deficient retinae, I identified a number of additional intrinsic and extrinsic regulatory pathway components whose expression is regulated by Id2a. These data highlight the integral role played by Id2a in the gene regulatory network governing the transition from retinoblast proliferation to terminal differentiation during vertebrate retinogenesis. / text