Faculty Bibliography

Telemedicine services facilitate the evaluation, diagnosis, and management of the remote patient. Telemedicine has rapidly flourished in the United States and has improved access to care, outcomes, and patient satisfaction. However, the use of telemedicine in ophthalmology is currently in its infancy and has yet to gain wide acceptance. Current models of telemedicine in ophthalmology are largely performed via "store and forward" methods, but remote monitoring and interactive modalities exist. Although studies have examined the effects of telemedicine, few reports have characterized its current status. We perform a descriptive analysis of the current state of teleophthalmology in the United States. We describe the use of teleophthalmology in the hospital and outpatient settings. We also review the applications to retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and glaucoma, as well as anticipated barriers and hurdles for the future adoption of teleophthalmology. With ongoing advances in teleophthalmology, these models may provide earlier detection and more reliable monitoring of vision-threatening diseases.

Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 x 10-27) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 x 10-5); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.European Journal of Human Genetics advance online publication, 30 August 2017; doi:10.1038/ejhg.2017.136.

PURPOSE/OBJECTIVE:To measure the waste generation and lifecycle environmental emissions from cataract surgery via phacoemulsification in a recognized resource-efficient setting. SETTING/METHODS:Two tertiary care centers of the Aravind Eye Care System in southern India. DESIGN/METHODS:Observational case series. METHODS:Manual waste audits, purchasing data, and interviews with Aravind staff were used in a hybrid environmental lifecycle assessment framework to quantify the environmental emissions associated with cataract surgery. Kilograms of solid waste generated and midpoint emissions in a variety of impact categories (eg, kilograms of carbon dioxide equivalents). RESULTS:Aravind generates 250 grams of waste per phacoemulsification and nearly 6 kilograms of carbon dioxide-equivalents in greenhouse gases. This is approximately 5% of the United Kingdom's phaco carbon footprint with comparable outcomes. A majority of Aravind's lifecycle environmental emissions occur in the sterilization process of reusable instruments because their surgical system uses largely reusable instruments and materials. Electricity use in the operating room and the Central Sterile Services Department (CSSD) accounts for 10% to 25% of most environmental emissions. CONCLUSIONS:Surgical systems in most developed countries and, in particular their use of materials, are unsustainable. Results show that ophthalmologists and other medical specialists can reduce material use and emissions in medical procedures using the system described here.

Background: Retinal imaging by optical coherence tomography (OCT) has gained increasing attention in multiple sclerosis and other neuroinflammatory and neurodegenerative disorders. Ambiguous and incomplete reporting of methodology and OCT-derived data have limited the ability to compare data and to apply and generalize findings in the past. To improve this situation, the Advised Protocol for Optical coherence tomography Study Terminology and Elements (APOSTEL) recommendations have been developed to outline core information to be provided when reporting quantitative OCT studies with help of a 9-point checklist (Cruz-Herranz and Balk et al., Neurology 2016). The APOSTEL recommendations currently have the evidence level of an expert opinion (Class IV). Objective: To advance the APOSTEL recommendations for OCT reporting in a formalized procedure towards evidence-based guidelines. Methods: Studies reporting quantitative OCT results published within the last 24 months have been identified by a Pubmed search. The corresponding authors of these 1472 articles will be contacted and asked to participate in an online survey to evaluate and give feedback on the initial APOSTEL recommendations. The feedback obtained will be anonymized and distributed to a panel of international experts for evaluation and revision of the recommendations. After the initial round the corresponding authors who gave feedback will be informed about the intermediate results and asked to participate in the survey for a second time. This procedure will be repeated if necessary following the consensus-building procedure of a DELPHI process. To this end, for each round the feedback obtained as well as any revisions made to the APOSTEL recommendations will be summarized and questionnaires will be used for evaluation in order to reach consensus and to develop evidencebased guidelines for prospective OCT studies. Results: The degree of consensus of the survey's participants will be reported for the initial and the revised versions of the recommendations as well as the revisions made to the initial version. Conclusion: Formal guidelines for the reporting of quantitative OCT studies will be presented as well as the process of how they were developed

Advances in imaging have made it increasingly common to study soft tissues without first embedding them in plastic or paraffin and without using labels or stains. The process, however, usually still involves fixation and cryosectioning, which could deform the tissues. Our goal was to quantify the morphological changes of ocular tissues caused by formalin fixation and cryosectioning. From each of 6 porcine eyes, 4 regions were obtained: cornea, equatorial and posterior sclera, and posterior pole containing the optic nerve head. Samples were imaged using visible light microscopy fresh, 1-minute and 24-hours post-fixation, and post-cryosectioning. Effects were assessed by 14 parameters representing sample size and shape. Overall, formalin fixation and sectioning caused only minimal changes to the ocular tissues, with average percentage parameter differences of 0.1%, 1%, and 1.2% between fresh and post-fixing by 1 minute, 24 hours, and post-cryosectioning, respectively. Parameter changes were not directional, and were only weakly dependent on the duration of fixation and the region of the eye. These results demonstrate that formalin fixation and cryosectioning are good choices for studying ocular tissue morphology and structure, as they do not cause the large tissue shrinkage or distortions typically associated with other, more complicated, techniques.

Glaucoma is a leading cause of blindness that leads to characteristic changes in the optic nerve head (ONH) region, such as nasalization of vessels. It is unknown whether the spatial location of this vessel shift inside the ONH occurs within the lamina cribrosa (LC) or the prelaminar tissue. The purpose of this study was to compare the location of the central retinal vessel trunk (CRVT) in the LC and prelaminar tissue in living healthy and glaucomatous eyes. We acquired 3-dimensional ONH scans from 119 eyes (40 healthy, 29 glaucoma suspect, and 50 glaucoma) using optical coherence tomography (OCT). The CRVT location was manually delineated in separate projection images of the LC and prelamina. We found that the CRVT in glaucoma suspect and glaucomatous eyes was located significantly more nasally compared to healthy eyes at the level of the prelamina. There was no detectable difference found in the location of the CRVT at the level of the LC between diagnostic groups. While the nasal location of the CRVT in the prelamina has been associated with glaucomatous axonal death, our results suggest that the CRVT in the LC is anchored in the tissue with minimal variation in glaucomatous eyes.

The purpose of this study was to characterize and determine the efficacy of a long-term, non-invasive gel/microsphere (GMS) eye drop for glaucoma. This novel drug delivery system is comprised of a thermoresponsive hydrogel carrier and drug-loaded polymer microspheres. In vitro release of brimonidine from the GMS drops and gel properties were quantified. A single brimonidine-loaded GMS drop was administered to 5 normotensive rabbits and intraocular pressure (IOP) was monitored for 28 days. Here we report that IOP reduction in rabbits receiving a single brimonidine GMS drop was comparable to that of rabbits receiving twice daily, standard brimonidine drops. GMS drops were retained in the inferior fornix in all animals for the length of the study. Our results suggest in vivo efficacy over 28 days from a single GMS drop and a potential decrease in systemic absorption, based on a lack of substantial IOP effects on the fellow untreated eye, compared to brimonidine twice-daily eye drops. To our knowledge, this represents the first long-term, drug-releasing depot that can be administered as a traditional eye drop.

Photoacoustic (PA) imaging detects acoustic signals generated by thermal expansion of a light-excited tissue or contrast agents. PA signal amplitude and image quality directly depend on the light fluence at the target depth. With conventional PA imaging systems, approximately 30% energy of incident light at the near-infrared region would be lost due to reflection on the skin surface. Such light loss directly leads to a reduction of PA signal and image quality. A new light delivery scheme that collects and redistributes reflected light energy was recently suggested, which is called the light catcher. In our previous study, proof of concept using a finite-element simulation model was shown and a laboratory-built prototype of the light catcher was applied on tissue-mimicking phantoms. In this paper, we present an elaborate prototype of a high-frequency PA probe with the light catcher fabricated using 3-D printing technology, which is conformal to a subcutaneous tumor in mice. The in vivo usefulness of the developed prototype was evaluated in a mouse tumor model. Equipped with the light catcher, PA signal amplitude from the clinical photosensitizer injected into the mouse tumor was enhanced by 33.7%, which is approximately equivalent to the percent light loss due to reflection on the skin.

Dry eye disease (DED) is a common ocular disorder affecting millions of individuals worldwide. The pathology of DED involves the infiltration of CD4⁺ lymphocytes, leading to tear film instability and destructive inflammation. In the healthy steady state, a population of immunosuppressive T-cells called regulatory T-cells (Treg) regulates proliferation of immune cells that would otherwise lead to a disruption of immunological homeostasis. For this reason, it has been suggested that Tregs could restore the immunological imbalance in DED. To this end, one possible approach would be to recruit the body's own, endogenous Tregs in order to enrich them at the site of inflammation and tissue destruction. Previously, we have demonstrated a reduction of inflammation and disease symptoms in models of periodontitis corresponding to recruitment of endogenous Tregs, which was accomplished by local placement of controlled release systems that sustain a gradient of the chemokine CCL22, referred to here as Treg-recruiting microspheres. Given that DED is characterized by a pro-inflammatory environment resulting in local tissue destruction, we hypothesized that the controlled release of CCL22 could also recruit Tregs to the ocular surface potentially mediating inflammation and symptoms of DED. Indeed, data suggest that Treg-recruiting microspheres are capable of overcoming the immunological imbalance of Tregs and CD4⁺ IFN-γ⁺ cells in the lacrimal gland. Administration of Treg-recruiting microspheres effectively mitigated the symptoms of DED as measured through a number of outcomes such as tear clearance, goblet cells density and corneal epithelial integrity, suggesting that recruitment of endogenous Treg can mitigate inflammation associated with DED.

Purpose: Although collagen microstructural crimp is a major determinant of ocular biomechanics, no direct measurements of optic nerve head (ONH) crimp have been reported. Our goal was to characterize the crimp period of the lamina cribrosa (LC) and peripapillary sclera (PPS) at low and normal IOPs. Methods: ONHs from 11 sheep eyes were fixed at 10-, 5-, or 0-mm Hg IOP and crimp periods measured manually from coronal cryosections imaged with polarized light microscopy (PLM). Using linear mixed-effect models, we characterized the LC and PPS periods, and how they varied with distance from the scleral canal edge. Results: A total of 17,374 manual collagen crimp period measurements were obtained with high repeatability (1.9 mum) and reproducibility (4.7 mum). The periods were smaller (P < 0.001) and less variable in the LC than in the PPS: average (SD) of 13.8 (3.1) mum in the LC, and 31.0 (10.4) mum in the PPS. LC crimp period did not vary with distance from the scleral canal wall (P > 0.1). PPS period increased with the square root of the distance to the canal (P < 0.0001). Conclusions: Small, uniform crimp periods within the sheep LC and immediately adjacent PPS may indicate that these tissues are setup to prevent large or heterogeneous deformations that insult the neural tissues within the canal. An increasing more variable period with distance from the canal provides a smooth transition of mechanical properties that minimizes stress and strain concentrations.