Publications

2018

Costela F, Saunders D, Kajtezovic S, Rose D, Woods R. Measuring the Difficulty Watching Video With Hemianopia and an Initial Test of a Rehabilitation Approach. Transl Vis Sci Technol. 2018;7(4):13.
Purpose: If you cannot follow the story when watching a video, then the viewing experience is degraded. We measured the difficulty of following the story, defined as the ability to acquire visual information, which is experienced by people with homonymous hemianopia (HH). Further, we proposed and tested a novel rehabilitation aid. Methods: Participants watched 30-second directed video clips. Following each video clip, subjects described the visual content of the clip. An objective score of information acquisition (IA) was derived by comparing each new response to a control database of descriptions of the same clip using natural language processing. Study 1 compared 60 participants with normal vision (NV) to 24 participants with HH to test the hypothesis that participants with HH would score lower than NV participants, consistent with reports from people with HH that describe difficulties in video watching. In the second study, 21 participants with HH viewed clips with or without a superimposed dynamic cue that we called a content guide. We hypothesized that IA scores would increase using this content guide. Results: The HH group had a significantly lower IA score, with an average of 2.8, compared with 4.3 shared words of the NV group (mixed-effects regression, < 0.001). Presence of the content guide significantly increased the IA score by 0.5 shared words ( = 0.03). Conclusions: Participants with HH had more difficulty acquiring information from a video, which was objectively demonstrated (reduced IA score). The content guide improved information acquisition, but not to the level of people with NV. Translational Relevance: The value as a possible rehabilitation aid of the content guide warrants further study that involves an extended period of content-guide use and a randomized controlled trial.
García-Posadas L, Hodges R, Diebold Y, Dartt DA. Context-Dependent Regulation of Conjunctival Goblet Cell Function by Allergic Mediators. Sci Rep. 2018;8(1):12162.
In the eye, goblet cells responsible for secreting mucins are found in the conjunctiva. When mucin production is not tightly regulated several ocular surface disorders may occur. In this study, the effect of the T helper (Th) 2-type cytokines IL4, IL5, and IL13 on conjunctival goblet cell function was explored. Goblet cells from rat conjunctiva were cultured and characterized. The presence of cytokine receptors was confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Changes in intracellular [Ca], high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with Th2 cytokines with or without the allergic mediator histamine. We found that IL4 and IL13 enhance cell proliferation and, along with histamine, stimulate goblet cell secretion. We conclude that the high levels of IL4, IL5, and IL13 that characterize allergic conjunctivitis could be the reason for higher numbers of goblet cells and mucin overproduction found in this condition.
Grundy S, Tshering L, Wanjala S, Diamond M, Audi M, Prasad S, Shinohara R, Rogo D, Wangmo D, Wangdi U, Aarayang A, Tshering T, Burke T, Mateen F. Retinal Parameters as Compared with Head Circumference, Height, Weight, and Body Mass Index in Children in Kenya and Bhutan. Am J Trop Med Hyg. 2018;99(2):482–488.
The retina shares embryological derivation with the brain and may provide a new measurement of overall growth status, especially useful in resource-limited settings. Optical coherence tomography (OCT) provides detailed quantification of retinal structures. We enrolled community-dwelling children ages 3-11 years old in Siaya, Kenya and Thimphu, Bhutan in 2016. We measured head circumference (age < 5 years only), height, and weight, and standardized these by age and gender. Research staff performed OCT (; Optovue, Inc., Fremont, CA), measuring the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) thicknesses. A neuro-ophthalmologist performed quality control for centration, motion artifact, and algorithm-derived quality scores. Generalized estimating equations were used to determine the relationship between anthropometric and retinal measurements. Two hundred and fifty-eight children (139 females, average age 6.4 years) successfully completed at least one retinal scan, totaling 1,048 scans. Nine hundred and twenty-two scans (88.0%) were deemed usable. Fifty-three of the 258 children (20.5%) were able to complete all six scans. Kenyan children had a thinner average GCC ( < 0.001) than Bhutanese children after adjustment for age and gender, but not RNFL ( = 0.70). In models adjusting for age, gender, and study location, none of standardized height, weight, and body mass index (BMI) were statistically significantly associated with RNFL or GCC. We determined that OCT is feasible in some children in resource-limited settings, particularly those > 4 years old, using the device. We found no evidence for GCC or RNFL as a proxy for height-, weight-, or BMI-for-age. The variation in mean GCC thickness in Asian versus African children warrants further investigation.
Harris D, Yamaguchi T, Hamrah P. A Novel Murine Model of Radiation Keratopathy. Invest Ophthalmol Vis Sci. 2018;59(10):3889–3896.
Purpose: Radiation therapy results in severe chronic keratopathy and dry eye disease. We developed a novel mouse model for radiation keratopathy to allow future mechanistic studies. Methods: Six to 8-week-old BALB/c mice underwent sublethal irradiation to the head only from a Cesium-137 irradiator, 2 × 550 rad, 3-hours apart. Irradiated mice were clinically evaluated by corneal fluorescein staining (CFS) at 1, 2, and 3 months, after which corneas were excised and immunofluorescence histochemistry performed with anti-CD45, anti-MHC class II, and anti-β-tubulin antibodies. Results: The survival rate after irradiation was 100%. Mice demonstrated significant CFS and hair loss around the eyes. Corneal nerve density decreased in the central and peripheral corneas (P < 0.01) at 2 and 3 months, respectively. CD45+ immune cell densities increased in the central and peripheral corneas (P < 0.005, P < 0.001) at 2 and 3 months, respectively. MHC class II, a sign of antigen presenting cell activation, significantly increased after irradiation in the central and peripheral corneas at 2 and 3 months (P = 0.02). A strong inverse correlation was noted between decreased corneal nerves and increase in CD45+ cells in the central cornea at 2 (P = 0.04, r = -0.89) and 3 months (P = 0.03, r = -0.91) after irradiation. Conclusions: We present a model of radiation keratopathy and demonstrate significant nerve loss and increase in immune cell influx and activation within months. This model will enable future investigations to understand the effects of radiation therapy on the eye, and to study mechanisms of neuro-immune crosstalk in the cornea.
Homer N, Fay A. Management of Long-Standing Flaccid Facial Palsy: Periocular Considerations. Otolaryngol Clin North Am. 2018;51(6):1107–1118.
Ineffective eyelid closure can pose a serious risk of injury to the ocular surface and eye. In cases of eyelid paresis, systematic examination of the eye and ocular adnexa will direct appropriate interventions. Specifically, 4 distinct periorbital regions should be independently assessed: eyebrow, upper eyelid, ocular surface, and lower eyelid. Corneal exposure can lead to dehydration, thinning, scarring, infection, perforation, and blindness. Long-term sequelae following facial nerve palsy may also include epiphora, gustatory lacrimation, and synkinesis.
Hoshi S, Okamoto F, Arai M, Hirose T, Sugiura Y, Murakami T, Oshika T. Patching retinal breaks with polyethylene glycol-based synthetic hydrogel sealant for retinal detachment in rabbits. Exp Eye Res. 2018;177:117–121.
The purpose of this study was to evaluate absorbable polyethylene glycol (PEG)-based synthetic hydrogel as a sealant for retinal breaks in rhegmatogenous retinal detachment (RD). A three-port, 25-gauge vitrectomy was performed on nine Dutch pigmented rabbit eyes. Subsequently, RD was induced by creating a retinal break. The retina was then reattached by fluid-air exchange. In six of nine eyes (RD-PEG group), PEG sealant was applied to completely cover the retinal breaks, and then photopolymerized with light; thereafter, intravitreous air was replaced with balanced salt solution (BSS). In the remaining three eyes (RD group), PEG sealant was not applied, but the intravitreous air was replaced with BSS. Ophthalmological examinations and intraocular pressure measurements were conducted preoperatively, and at 1 and 7 days, and 1, 3, and 6 months postoperatively. Histological examinations of the eyes were performed after 6 postoperative months. At surgery, retinal reattachment with PEG sealant was achieved in all eyes in the RD-PEG group. Fundoscopic and optical coherence tomographic examinations revealed that the retina remained attached in all the eyes of the RD-PEG group throughout the 6-month observation period. Histological examination revealed no signs of damage in the retinal layers at the edges of the retinal breaks that were in contact with the sealant. In the RD group, the retinas detached in all eyes within 7 days postoperatively. The PEG sealant closed the retinal breaks and maintained retinal reattachment. Intraocular tamponade was not necessary.
SIGNIFICANCE: The first report on the use of peripheral prisms (p-prisms) for patients with left neglect and homonymous visual field defects (HVFDs). PURPOSE: The purpose of this study was to investigate if patients with left hemispatial neglect and HVFDs benefit from p-prisms to expand the visual field and improve obstacle detection. METHODS: Patients (24 with HVFDs, 10 of whom had left neglect) viewed an animated, virtual, shopping mall corridor and reported if they would have collided with a human obstacle that appeared at various offsets up to 13.5° from their simulated walking path. There were 40 obstacle presentations on each side, with and without p-prisms. No training with p-prisms was provided, and gaze was fixed at the center of expansion. RESULTS: Detection on the side of the HVFD improved significantly with p-prisms in both groups, from 26 to 92% in the left-neglect group and 43 to 98% in the non-neglect group (both P < .001). There was a tendency for greater improvement in the neglect patients with p-prisms. For collision judgments, both groups exhibited a large increase in perceived collisions on the side of the HVFD with the prisms (P < .001), with no difference between the groups (P = .93). Increased perceived collisions represent a wider perceived safety margin on the side of the HVFD. CONCLUSIONS: Within the controlled conditions of this simulated, collision judgment task, patients with left neglect responded well to initial application of p-prisms exhibiting improved detection and wider safety margins on the side of the HVFD that did not differ from non-neglect patients. Further study of p-prisms for neglect patients in free-gaze conditions after extended wear and in real-world mobility tasks is clearly warranted.
Hudry E, Andres-Mateos E, Lerner E, Volak A, Cohen O, Hyman B, Maguire C, Vandenberghe L. Efficient Gene Transfer to the Central Nervous System by Single-Stranded Anc80L65. Mol Ther Methods Clin Dev. 2018;10:197–209.
Adeno-associated viral vectors (AAVs) have demonstrated potential in applications for neurologic disorders, and the discovery that some AAVs can cross the blood-brain barrier (BBB) after intravenous injection has further expanded these opportunities for non-invasive brain delivery. Anc80L65, a novel AAV capsid designed from reconstruction of the viral evolutionary lineage, has previously demonstrated robust transduction capabilities after local delivery in various tissues such as liver, retina, or cochlea, compared with conventional AAVs. Here, we compared the transduction efficacy of Anc80L65 with conventional AAV9 in the CNS after intravenous, intracerebroventricular (i.c.v.), or intraparenchymal injections. Anc80L65 was more potent at targeting the brain and spinal cord after intravenous injection than AAV9, and mostly transduced astrocytes and a wide range of neuronal subpopulations. Although the efficacy of Anc80L65 and AAV9 is similar after direct intraparenchymal injection in the striatum, Anc80L65's diffusion throughout the CNS was more extensive than AAV9 after i.c.v. infusion, leading to widespread expression in the cerebellum. These findings demonstrate that Anc80L65 is a highly efficient gene transfer vector for the murine CNS. Systemic injection of Anc80L65 leads to notable expression in the CNS that does not rely on a self-complementary genome. These data warrant further testing in larger animal models.
Jung JH, Peli E. Field Expansion for Acquired Monocular Vision Using a Multiplexing Prism. Optom Vis Sci. 2018;95(9):814–828.
SIGNIFICANCE: Acquired monocular vision (AMV) is a common visual field loss. Patients report mobility difficulties in walking due to collisions with objects or other pedestrians on the blind side. PURPOSE: The visual field of people with AMV extends more than 90° temporally on the side of the seeing eye but is restricted to approximately 55° nasally. We developed a novel field expansion device using a multiplexing prism (MxP) that superimposes the see-through and shifted views for true field expansion without apical scotoma. We present various designs of the device that enable customized fitting and improved cosmetics. METHODS: A partial MxP segment is attached (base-in) near the nose bridge. To avoid total internal reflection due to the high angle of incidence at nasal field end (55°), we fit the MxP with serrations facing the eye and tilt the prism base toward the nose. We calculated the width of the MxP (the apex location) needed to prevent apical scotoma and monocular diplopia. We also consider the effect of spectacle prescriptions on these settings. The results are verified perimetrically. RESULTS: We documented the effectivity of various prototype glasses designs with perimetric measurements. With the prototypes, all patients with AMV had field-of-view expansions up to 90° nasally without any loss of seeing field. CONCLUSIONS: The novel and properly mounted MxP in glasses has the potential for meaningful field-of-view expansion up to the size of normal binocular vision in cosmetically acceptable form.
Jung JH, Peli E. No Useful Field Expansion with Full-field Prisms. Optom Vis Sci. 2018;95(9):805–813.
SIGNIFICANCE: Full-field prisms that fill the entire spectacle eye wire have been considered as field expansion devices for homonymous hemianopia (HH) and acquired monocular vision (AMV). Although the full-field prism is used for addressing binocular dysfunction and for prism adaptation training after brain injury as treatment for spatial hemineglect, we show that the full-field prism for field expansion does not effectively expand the visual field in either HH or AMV. PURPOSE: Full-field prisms may shift a portion of the blind side to the residual seeing side. However, foveal fixation on an object of interest through a full-field prism requires head and/or eye rotation away from the blind side, thus negating the shift of the field toward the blind side. METHODS: We fit meniscus and flat full-field 7Δ and 12Δ yoked prisms and conducted Goldmann perimetry in HH and AMV. We compared the perimetry results with ray tracing calculations. RESULTS: The rated prism power was in effect at the primary position of gaze for all prisms, and the meniscus prisms maintained almost constant power at all eccentricities. To fixate on the perimetry target, the subjects needed to turn their head and/or eyes away from the blind side, which negated the field shift into the blind side. In HH, there was no difference in the perimetry results on the blind side with any of the prisms. In AMV, the lower nasal field of view was slightly shifted into the blind side with the flat prisms, but not with the meniscus prisms. CONCLUSIONS: Full-field prisms are not an effective field expansion device owing to the inevitable fixation shift. There is potential for a small field shift with the flat full-field prism in AMV, but such lenses cannot incorporate refractive correction. Furthermore, in considering the apical scotoma, the shift provides a mere field substitution at best.