Case Report: Novel Patient Training Technique for the Application and Removal of Scleral Lenses.

SIGNIFICANCE: This report shares a technique that can be used to assist training patients to properly and safely apply and remove prosthetic replacement of the ocular surface ecosystem devices (PD) or scleral lenses to reduce patient training nervousness, limit adverse events from training, and limit training failures. PURPOSE: This study aimed to introduce a novel scleral lens application and removal training method. CASE REPORT: A 28-year-old woman with limbal stem cell deficiency secondary to contact lens overwear in the left eye greater than the right eye presented for prosthetic replacement of the ocular surface ecosystem treatment. Her ocular history included herpes simplex keratitis, fungal keratitis, and acanthamoeba keratitis in the left eye, which ultimately resulted in corneal perforation requiring repair with cyanoacrylate adhesive. The patient was initially fitted with a PD in 2015 in the left eye but had difficulty with application of the device on the eye, which resulted in discontinuation of use. She returned to the clinic in 2021 for a reevaluation and PD refitting. To address her past difficulties surrounding application and removal of the device, a novel piggyback technique (applying a second scleral lens on top of the primary customized scleral lens that is already on the eye) was used to successfully train the patient. CONCLUSIONS: A novel piggyback training technique can be used to overcome obstacles during the scleral lens application and removal training process.

PROSE treatment for lagophthalmos and exposure keratopathy.

Prosthetic replacement of the ocular surface ecosystem is a treatment developed by the Boston Foundation for Sight that uses a Food and Drug Administration-approved prosthetic device for the treatment of severe ocular surface disease to improve vision and discomfort in addition to supporting the ocular surface. Facial nerve paralysis has multiple causes including trauma, surgery, tumor, stroke, and congenital lagophthalmos. Subsequent lagophthalmos leading to exposure keratitis has been treated with copious lubrication, tarsorrhapy, eyelid weights, chemodenervation to yield protective ptosis, and palpebral spring insertion. Each of these treatments, however, has limitations and potential complications. The prosthetic replacement of the ocular surface ecosystem device provides a liquid bandage to protect the cornea from eyelid interaction and dessication in addition to improving vision. This report describes 4 patients with exposure keratitis who were successfully treated with prosthetic replacement of the ocular surface ecosystem devices at 2 clinical sites.

Use of PROSE for long-term ocular surface support in patients with a permanent keratoprosthesis.

Purpose: To describe the long-term outcome of the use of a specialized scleral lens known as a prosthetic replacement of the ocular surface ecosystem (PROSE) device to support the ocular surface in patients with a Boston Keratoprosthesis (KPro) Type I. All patients in this series were unable to pursue continuous wear of a bandage soft contact lens (BSCL) - a critical aspect of post KPro implantation management intended to protect the corneal carrier tissue from desiccation and stromal melting. Observations: Four eyes of four patients with a Boston KPro Type I were included. All four had failed BSCL wear and were instead treated with PROSE device wear. All four patients had underlying diagnoses associated with a diseased ocular surface (Stevens-Johnson Syndrome [one patient], prior failed penetrating keratoplasty associated with herpes zoster-related neurotrophic keratopathy [one patient], and prior failed penetrating keratoplasty associated with severe dry eye disease [two patients]). Causes of failure of BSCL wear included poor retention, discomfort, and poor vision. PROSE device wear was initiated on average seven and a half (range four to 14) months post-KPro implantation. The wear schedule varied and ranged from waking-hour wear only to 24-h wear. The average duration of device wear was 59.3 (range 28-103) months. Two patients exhibited persistent corneal epithelial defect formation with waking-hour wear, which resolved within 10 days with 24-h device wear. All patients exhibited improvement in vision with PROSE compared to baseline, averaging six and a half (range six to eight) lines of improvement in Snellen acuity, and all patients reported increased comfort. There was no incidence of microbial keratitis, KPro device instability, or other complication throughout the duration of device wear. Conclusions and Importance: This report offers a novel alternate approach to long-term support of the ocular surface in patients with a Boston KPro who fail standard continuous BSCL wear.

Ocular Graft-versus-Host Disease Underdiagnosis: A Survey Study.

Purpose: To understand the degree and explore the possible causes of ocular graft-versus-host disease (oGVHD) underdiagnosis in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and Methods: A 15-question survey was emailed to 6032 subscribers to the Blood and Marrow Transplant Information Network. A total of 371 respondents confirmed the history of allo-HSCT, of which 335 were symptomatic. Their self-reported symptoms, onset, treatments tried, degree of symptom control and established diagnoses of systemic chronic graft-versus-host disease (cGVHD) and oGVHD were analyzed. Results: Among the 335 symptomatic survey respondents, 306 reported their ocular symptom onset was after allo-HSCT, with only 170 [55.6% (170/306)] ever receiving a diagnosis of oGVHD; 23 reported worsening pre-existing ocular symptoms after allo-HSCT, with only 5 [21.7% (5/23)] ever receiving a diagnosis of oGVHD; 6 reported stable symptoms before and after allo-HSCT, with 1 ever receiving a diagnosis of oGVHD. Of the 176 respondents carrying the diagnosis of oGVHD, 167 [94.9% (167/176)] also had the diagnosis of cGVHD. Logistic regression analysis showed that the diagnosis of oGVHD was highly correlated with the number of symptoms and treatments one reported. Furthermore, 35% of the respondents with new onset ocular symptoms reported onset within the first 6 months after allo-HSCT (previously reported), as well as 39% of the respondents with worsened existing symptoms. Conclusion: oGVHD underdiagnosis is likely associated with the previous diagnostic criteria, in which cGVHD of another organ system was required. The correct notion that oGVHD commonly causes severe dry eye disease has likely led to its underdiagnosis in patients with fewer number of symptoms and/or who tried fewer treatments.

Trends in wildlife rehabilitation rescues and animal fate across a six-year period in New South Wales, Australia.

Globally, millions of animals are rescued and rehabilitated by wildlife carers each year. Information gathered in this process is useful for uncovering threats to native wildlife, particularly those from anthropogenic causes. However, few studies using rehabilitation data include a diverse range of fauna, cover large geographical areas, and consider long-term trends. Furthermore, few studies have statistically modelled causes of why animals come into care, and what are their chances of survival. This study draws on 469,553 rescues reported over six years by wildlife rehabilitators for 688 species of bird, reptile, and mammal from New South Wales, Australia. For birds and mammals, 'abandoned/orphaned' and 'collisions with vehicles' were the dominant causes for rescue, however for reptiles this was 'unsuitable environment'. Overall rescue numbers were lowest in winter, and highest in spring, with six-times more 'abandoned/orphaned' individuals in spring than winter. Of the 364,461 rescues for which the fate of an animal was known, 92% fell within two categories: 'dead', 'died or euthanased' (54.8% of rescues with known fate) and animals that recovered and were subsequently released (37.1% of rescues with known fate). Modelling of the fate of animals indicated that the likelihood of animal survival (i.e. chance of: being released, left and observed, or permanent care), was related to the cause for rescue. In general, causes for rescue involving physical trauma (collisions, attacks, etc.) had a much lower likelihood of animals surviving than other causes such as 'unsuitable environment', 'abandoned/orphaned', and this also showed some dependence upon whether the animal was a bird, reptile, or mammal. This suggests rehabilitation efforts could be focused on particular threats or taxa to maximise success, depending on the desired outcomes. The results illustrate the sheer volume of work undertaken by rehabilitation volunteers and professionals toward both animal welfare and to the improvement of wildlife rehabilitation in the future.

Scleral Lens and Prosthetic Replacement of the Ocular Surface Ecosystem Utilization in Ocular Graft-versus-Host Disease: A Survey Study.

PURPOSE: To evaluate the utilization of scleral lenses and prosthetic replacement of the ocular surface ecosystem devices (SL/PDs) in the management of ocular graft-versus-host disease (oGVHD). PATIENTS AND METHODS: A survey of 15 questions was sent via email to 6032 subjects registered with the Blood and Marrow Transplant Information Network. The survey reviewed transplant history, graft-versus-host disease history, as well as oGVHD symptoms and onset. Additional questions surveyed treatments used for oGVHD, as well as the degree of ocular symptom control and experience with SL/PDs. A total of 306 respondents met the eligibility requirements to be part of the analyzed cohort. RESULTS: The mean number of symptoms reported from the analyzed cohort was 4.79 ± 2.44, median (IQR) of 5.0 (3.0 to 7.0), with the most common symptom being gritty, dry eyes (87%). The mean number of treatments utilized across the analyzed cohort was 3.21 ± 2.55, median (IQR) of 2.5 (1.0 to 5.0), with the most common treatment being artificial tears (86%). Wearing scleral lenses resulted in a mean of 5.42 ± 1.86, median (IQR) of 6.0 (4.0 to 7.0) symptoms improving, with improved dryness/grittiness of the eyes (94%), improved eye pain (92%) and improved quality of life (89%) being the most commonly improved symptoms. Fifty-six percent of those wearing scleral lenses wished the lenses had been recommended sooner. The most common reason patients cited for not wearing scleral lenses was that they had never heard of them (63%). CONCLUSION: SL/PDs help to control the symptoms of oGVHD. With their use, clinicians are able to improve the quality of life of this patient population. Despite the known benefits, SL/PDs still remain underutilized in oGVHD care. A majority of current SL/PD wearers wish that they had been recommended sooner as a treatment option. SL/PDs should be considered a component of comprehensive oGVHD management.

Unilateral pediatric neurotrophic keratitis due to congenital left trigeminal nerve aplasia with PROSE (prosthetic replacement of the ocular surface ecosystem) treatment.

PURPOSE: To present a 3-year-old female patient with a non-familial, isolated, unilateral case of left corneal anesthesia with MRI-confirmed congenital left trigeminal nerve aplasia. OBSERVATIONS: A corneal epithelial defect was noted in the left eye after an 8-week trial of recombinant human nerve growth factor. Subsequent evaluation and fitting of a PROSE (prosthetic replacement of the ocular surface ecosystem) lens led to healing of the corneal epithelium and visual acuity improvement from 20/300 to 20/70. CONCLUSIONS AND IMPORTANCE: A scleral lens may be a possible treatment for those with neurotrophic keratitis in which a trial of topical lubrication and human nerve growth factor has not been effective.

Conceptual dissonance: evaluating the efficacy of natural language processing techniques for validating translational knowledge constructs.

The conduct of large-scale translational studies presents significant challenges related to the storage, management and analysis of integrative data sets. Ideally, the application of methodologies such as conceptual knowledge discovery in databases (CKDD) provides a means for moving beyond intuitive hypothesis discovery and testing in such data sets, and towards the high-throughput generation and evaluation of knowledge-anchored relationships between complex bio-molecular and phenotypic variables. However, the induction of such high-throughput hypotheses is non-trivial, and requires correspondingly high-throughput validation methodologies. In this manuscript, we describe an evaluation of the efficacy of a natural language processing-based approach to validating such hypotheses. As part of this evaluation, we will examine a phenomenon that we have labeled as "Conceptual Dissonance" in which conceptual knowledge derived from two or more sources of comparable scope and granularity cannot be readily integrated or compared using conventional methods and automated tools.

Integrating web portlet technologies with caGrid to enable rapid application development: the CRC Patient Study Calendar.

The caGrid middleware provides an extensible platform for the integration of heterogeneous data sources and services; such as those found in geographically distributed research consortia. We describe an architectural approach to the integration of web portlet technologies with caGrid in order to facilitate the rapid development of highly usable presentation models for grid-based data sources and services, using the development of a patient study calendar for the CLL Research Consortium as a motivating use case.

Ontology-anchored Approaches to Conceptual Knowledge Discovery in a Multi-dimensional Research Data Repository.

Chronic Lymphocytic Leukemia (CLL) is the most common adult leukemia in the U.S., and is currently incurable. Though a small number of biomarkers that may correlate to risk of disease progression or treatment outcome in CLL have been discovered, few have been validated in prospective studies or adopted in clinical practice. In order to address this gap in knowledge, it is desirable to discover and test hypotheses that are concerned with translational biomarker-to-phenotype correlations. We report upon a study in which commonly available ontologies were utilized to support the discovery of such translational correlations. We have specifically applied a technique known as constructive induction to reason over the contents of a research data repository utilized by the NCI-funded CLL Research Consortium. Our findings indicate that such an approach can produce semantically meaningful results that can inform hypotheses about higher-level relationships between the types of data contained in such a repository.

Supporting the design of translational clinical studies through the generation and verification of conceptual knowledge-anchored hypotheses.

The ability to generate hypotheses based upon the contents of large-scale, heterogeneous data sets is critical to the design of translational clinical studies. In previous reports, we have described the application of a conceptual knowledge engineering technique, known as constructive induction (CI) in order to satisfy such needs. However, one of the major limitations of this method is the need to engage multiple subject matter experts to verify potential hypotheses generated using CI. In this manuscript, we describe an alternative verification technique that leverages published biomedical literature abstracts. Our report will be framed in the context of an ongoing project to generate hypotheses related to the contents of a translational research data repository maintained by the CLL Research Consortium. Such hypotheses will are intended to inform the design of prospective clinical studies that can elucidate the relationships that may exist between biomarkers and patient phenotypes.