Deficiency in Acyl-CoA:Wax Alcohol Acyltransferase 2 causes evaporative dry eye disease by abolishing biosynthesis of wax esters.

Lipids secreted by the meibomian glands (MGs) of the eyelids are essential to the protection of the eye's surface. An altered meibum composition represents the primary cause of evaporative dry eye disease (DED). Despite the critical importance of the meibum, its biosynthetic pathways and the roles of individual lipid components remain understudied. Here, we report that the genetic deletion of Acyl-CoA:wax alcohol acyltransferase 2 (AWAT2) causes the obstruction of MGs and symptoms of evaporative DED in mice. The lipid composition of the meibum isolated from Awat2-/- mice revealed the absence of wax esters, which was accompanied by a compensatory overproduction of cholesteryl esters. The resulting increased viscosity of meibum led to the dilation of the meibomian ducts, and the progressive degeneration of the MGs. Overall, we provide evidence for the main physiological role of AWAT2 and establish Awat2-/- mice as a model for DED syndrome that can be used in studies on tear film-oriented therapies.

Chronic Conjunctivitis From a Retained Contact Lens.

PURPOSE: To help clinicians diagnose and manage unilateral recalcitrant chronic bacterial conjunctivitis secondary to a retained soft contact lens and describe the first report of Gram-negative bacteria causing this condition. METHODS: Chart review of successive cases presenting with unilateral chronic conjunctivitis with positive cultures and a retained contact lens. RESULTS: Three cases were identified and described. Culturing of the retained contact lenses grew Pseudomonas aeruginosa in the first case, Achromobacter xylosoxidans in the second, and Staphylococcus epidermidis in the third. All three patients were successfully treated with removal of the retained lens and targeted antibiotic eyedrop therapy. CONCLUSIONS: Unilateral chronic recurrent or recalcitrant purulent papillary conjunctivitis is rare, and a retained contact lens should be suspected in patients with a history of wearing contact lenses. Careful examination with double eversion of the upper eyelid and sweeping of the fornices can recover the offending lens. Although only Gram-positive organisms have been isolated in previous reports, two of our three cultures grew Gram-negative organisms, highlighting the importance of broad-spectrum antibiotic usage for these cases.

Successful Management of Corneal Neuropathic Pain with Intrathecal Targeted Drug Delivery.

OBJECTIVE: To describe the successful treatment of refractory corneal neuropathic pain with neuromodulation techniques. DESIGN: Single case report. SETTING: Academic tertiary care center in the United States of America. SUBJECT AND METHODS: A 30-year-old woman presented with a 7-year history of refractory bilateral keratoneuralgia following laser-assisted in-situ keratomileusis (LASIK) procedure on both eyes. Having failed all conservative measures, the patient initially underwent trigeminal nerve stimulation and subsequently was implanted with an intrathecal drug delivery system (IDDS) with the catheter placed at the level C1. RESULTS: Following an initial favorable response to the trigeminal nerve stimulator, the pain became refractory to neurostimulation after a few months and the system was explanted. The patient was successfully trialed with an intrathecal catheter placed at the level of C1 delivering a combination of bupivacaine and low dose fentanyl. The patient was then implanted with an IDDS equipped with a patient-activated bolus system. The patient was very satisfied with the treatment and has had greater than 50% pain relief for over a year. CONCLUSIONS: Intrathecal delivery of bupivacaine and low dose fentanyl in the upper cervical spine can be effective in controlling refractory eye pain in properly selected patients and treatment centers.

The Boston keratoprosthesis provides a wide depth of focus.

PURPOSE: To measure the through-focus curve for eyes implanted with a type 1 Boston keratoprosthesis (KPro) and compare it to that of pseudophakic controls with fixed pupil sizes. The results should assist in evaluating postoperative visual quality after surgery. They should also help to determine the necessary KPro inventories in terms of refractive power steps. METHODS: Autorefraction and manifest refraction were performed on all eyes. The monocular through-focus acuity curve was plotted in reference to the best-corrected visual acuity by spectacle plane defocus ranging from +5.00 to -5.00 dioptres in 0.50 dioptre increments. These measurements were obtained on KPro-implanted eyes, pseudophakic eyes as controls, and on the same control eyes after fixing the pupil diameter to 3 and 2 mm using black painted iris contact lenses. RESULTS: Ten KPro eyes and five control eyes were included. Good agreement was noted between the subjective refractions and autorefraction in KPro eyes. The average through-focus curve for the control eyes was significantly steeper than that of the KPro curve, but became comparable after fixing the control pupil to 2 and 3 mm. CONCLUSION: The KPro's wide depth-of-focus makes the visual acuity less dependent on an exact refractive correction at distance and explains the 'pseudoaccomodation' experienced by these patients. This is primarily due to the small pupil diameter of the KPro. The current manufacturing steps in 0.50 dioptre increments appears to be sufficient.

Ergonomic considerations for the modern radiology practice: An update.

The average post-pandemic modern radiology practice is experiencing an ever-increasing workload volume with overall relatively similar staffing levels, regardless of practice setting. This has resulted in an increased workload demand for the average diagnostic radiologist, which in many cases translates to longer working hours. It is now more important than ever to be cognizant of various work-related injuries, including repetitive-stress injuries and vision-related ailments as examples, in relation to the working conditions of the radiologist. This article will discuss commonly occurring conditions and ergonomic considerations that the radiologist can employ to reduce the risk of work-related injuries.

Wide-angle fundus imaging through the Boston keratoprosthesis.

PURPOSE: To explore the feasibility and compare the outcomes of three wide-angle fundus cameras for imaging the peripheral retina through the Type 1 Boston keratoprosthesis. METHODS: The noncontact Optos and the contact RetCam and Panoret wide-angle imaging systems were used to image the retina of eyes implanted with a keratoprosthesis. The failure-to-image rate, ease of acquisition, and quality of the images were noted, and the field of view was compared. Limitations and complications were recorded. Optos was then performed on patients referred for ultrasound B-scan evaluation, and the imaging findings were correlated. RESULTS: Retinal images with all three cameras were obtained on four eyes. Optos could be performed on all four eyes, RetCam on three, and Panoret on two. The field of view was comparable between the three different cameras. The best quality images were obtained with Optos. The external illumination of the Panoret made it impossible to image the only darkly pigmented individual in the series. Both contact devices failed to image another patient who was too agitated. Two patients had some ocular irritation from the coupling agent that resolved with replacement of the contact lens. Optos images were obtained on an additional six eyes, and findings correlated well with those on B-scan. Optos was superior to B-scan in an eye with silicone oil filling. CONCLUSION: Wide-angle fundus imaging through the keratoprosthesis is possible, and all three cameras performed similarly. The good quality of pictures obtained with the noncontact Optos, as well as its ease of use, comfort, and safety make it a preferred choice. Optos complements B-scan in the examination of the peripheral retina through the keratoprosthesis, and it may even be superior in certain settings.

TFOS Lifestyle: Impact of the digital environment on the ocular surface.

Eye strain when performing tasks reliant on a digital environment can cause discomfort, affecting productivity and quality of life. Digital eye strain (the preferred terminology) was defined as "the development or exacerbation of recurrent ocular symptoms and/or signs related specifically to digital device screen viewing". Digital eye strain prevalence of up to 97% has been reported, due to no previously agreed definition/diagnostic criteria and limitations of current questionnaires which fail to differentiate such symptoms from those arising from non-digital tasks. Objective signs such as blink rate or critical flicker frequency changes are not 'diagnostic' of digital eye strain nor validated as sensitive. The mechanisms attributed to ocular surface disease exacerbation are mainly reduced blink rate and completeness, partial/uncorrected refractive error and/or underlying binocular vision anomalies, together with the cognitive demand of the task and differences in position, size, brightness and glare compared to an equivalent non-digital task. In general, interventions are not well established; patients experiencing digital eye strain should be provided with a full refractive correction for the appropriate working distances. Improving blinking, optimizing the work environment and encouraging regular breaks may help. Based on current, best evidence, blue-light blocking interventions do not appear to be an effective management strategy. More and larger clinical trials are needed to assess artificial tear effectiveness for relieving digital eye strain, particularly comparing different constituents; a systematic review within the report identified use of secretagogues and warm compress/humidity goggles/ambient humidifiers as promising strategies, along with nutritional supplementation (such as omega-3 fatty acid supplementation and berry extracts).

Association Between Depression and Severity of Dry Eye Symptoms, Signs, and Inflammatory Markers in the DREAM Study.

Importance: Depression is more prevalent in patients with dry eye disease (DED) than in the general population; however, the association between severity of DED and depression needs further evaluation. Objective: To investigate the association between depression and severity of DED symptoms and signs, including inflammatory markers. Design, Setting, and Participants: Secondary cross-sectional and longitudinal analysis performed in April to December 2020 of data from Dry Eye Assessment and Management (DREAM) study, a randomized clinical trial from October 2014 to July 2016 including patients with moderate to severe symptoms and signs of DED. Enrolled from 27 ophthalmology and optometry centers, both academic and private, in 17 US states, 535 patients were followed up for 1 year. Exposure: Participants screened positive for depression if they scored 42 or less on the Mental Component Summary (MCS) of the 36-Item Short Form Health Survey. Main Outcomes and Measures: Symptoms of DED were assessed by Ocular Surface Disease Index (OSDI) and Brief Ocular Discomfort Index (BODI) and signs assessed by tear film breakup time, Schirmer test, corneal and conjunctival staining, tear osmolarity, and meibomian gland dysfunction at baseline, 6 months, and 12 months. A composite severity sign score was calculated from all 6 signs. Inflammatory markers (cytokines in tears and HLA-DR expression by conjunctival surface cells) were measured for some trial participants. Features of DED were compared between participants with and without depression and adjusted for age, sex, race, visits, and baseline comorbidities. Results: Among the 535 participants, mean (SD) age was 58 (13.2) years, 434 participants (81%) were women, and 398 (74.4%) were White. Participants who screened positive for depression had worse DED symptoms by OSDI (effect size = 0.45, P < .001) and BODI (effect size = 0.46, P < .001) and composite DED sign score (effect size = 0.21, P = .006). Lower MCS score (ie, worse depression) was correlated with higher OSDI score (ie, worse DED symptoms) at baseline (Spearman ρ = -0.09, P = .03), 6 months (ρ = -0.20, P < .001), and 12 months (ρ = -0.21, P < .001). Inflammatory markers did not differ by depression status. Conclusions and Relevance: Depression was associated with more severe dry eye symptoms and overall signs, suggesting that among patients with moderate to severe DED, those with depression may be likely to have more severe DED. These findings support consideration of depression as a comorbidity when managing patients with DED. Further study is needed to elucidate the relationship.

Diffuse retinal injury from a non-penetrating TASER dart.

To describe a non-penetrating TASER gun injury resulting in a small exudative retinal detachment but significant visual acuity and retinal function loss as demonstrated by electroretinography (ERG). A 39-year-old man presented to the emergency department with a TASER barb embedded in his right lower lid. A complete clinical ophthalmologic examination and surgical extrication were performed, as well as radiologic imaging and Ganzfeld electroretinography. No scleral penetration was observed on surgical exploration. Retinal examination showed a peripheral exudative detachment. Subsequent follow-up revealed progressive resolution of the detachment and improvement in visual acuity. The ERG showed a 63-70% decrease in rod a- and b-waves, while isolated cone responses were reduced by only 10%, with a minimal increase in implicit time. This case shows that periocular TASER injuries, even if apparently superficial, may result in significant ocular damage. ERG may be useful in the diagnosis of visual loss attributed to disturbance in photoreceptor function, in the absence of anatomically evident damage.

Novel mechanism of decreased iris vasculature density after cosmetic iris implants.

A 25-year-old man presented with decreased vision in both eyes, approximately 4 years following bilateral bright ocular cosmetic iris implantation. On examination, he was found to have bilateral elevated intraocular pressures, anterior chamber cells and flare, chronic peripheral anterior synechiae and significantly reduced endothelial cell counts. Ultrasound biomicroscopy demonstrated compression of the peripheral iris, resulting in synechial angle closure in both eyes. Surgical removal of the implants was performed without additional complication. On removal, bilateral iris atrophy was evident with non-reacting pupils and permanent mydriasis. Optical coherence tomography angiography showed a reduction in iris vasculature density that is more pronounced in the area of the iris atrophic defects. This case suggests that cosmetic iris implants may compress iris vasculature, resulting in decreased iris perfusion resulting in atrophic mydriasis and iris defects. This is a potential novel mechanism for complications in eyes with cosmetic iris implants.

Ocular Discomfort and Quality of Life Among Patients in the Dry Eye Assessment and Management Study.

PURPOSE: To assess the association of severity of ocular discomfort with measures of quality of life among patients with moderate to severe dry eye disease (DED). METHODS: This is a prospective, observational, cohort study within a randomized clinical trial. Patients (N = 535) in the Dry Eye Assessment and Management study with moderate to severe DED completed the Ocular Surface Disease Index on DED symptoms, the SF-36 on quality of life, and the Brief Ocular Discomfort Inventory questionnaire and had a comprehensive ophthalmic assessment by a study-certified clinician. The ocular discomfort on average over the past week was scored on an 11-point scale (0 for no discomfort and 10 for discomfort as bad as you can imagine). RESULTS: The average ocular discomfort scores for patients ranged from 0 to 10, with a mean of 4.28. Discomfort scores did not vary with demographic characteristics, signs of DED, self-reported depression, or self-reported nonocular pain conditions. Ocular discomfort scores did correlate moderately to strongly with total Ocular Surface Disease Index scores (Spearman correlation coefficient, rs, 0.47-0.67) and with measures of interference with activities of daily living [general activity level, mood, walking ability, ability for normal work, relations with other people, sleep, and enjoyment of life (rs = 0.39-0.65)]. CONCLUSIONS: Among patients in the Dry Eye Assessment and Management study, worse ocular discomfort was associated with worse overall DED symptoms and interfered to a greater degree with activities of daily living. Ocular discomfort is an important part of the assessment of patients with DED.

FaceGuard: A Wearable System To Avoid Face Touching.

Most people touch their faces unconsciously, for instance to scratch an itch or to rest one's chin in their hands. To reduce the spread of the novel coronavirus (COVID-19), public health officials recommend against touching one's face, as the virus is transmitted through mucous membranes in the mouth, nose and eyes. Students, office workers, medical personnel and people on trains were found to touch their faces between 9 and 23 times per hour. This paper introduces FaceGuard, a system that utilizes deep learning to predict hand movements that result in touching the face, and provides sensory feedback to stop the user from touching the face. The system utilizes an inertial measurement unit (IMU) to obtain features that characterize hand movement involving face touching. Time-series data can be efficiently classified using 1D-Convolutional Neural Network (CNN) with minimal feature engineering; 1D-CNN filters automatically extract temporal features in IMU data. Thus, a 1D-CNN based prediction model is developed and trained with data from 4,800 trials recorded from 40 participants. Training data are collected for hand movements involving face touching during various everyday activities such as sitting, standing, or walking. Results showed that while the average time needed to touch the face is 1,200 ms, a prediction accuracy of more than 92% is achieved with less than 550 ms of IMU data. As for the sensory response, the paper presents a psychophysical experiment to compare the response time for three sensory feedback modalities, namely visual, auditory, and vibrotactile. Results demonstrate that the response time is significantly smaller for vibrotactile feedback (427.3 ms) compared to visual (561.70 ms) and auditory (520.97 ms). Furthermore, the success rate (to avoid face touching) is also statistically higher for vibrotactile and auditory feedback compared to visual feedback. These results demonstrate the feasibility of predicting a hand movement and providing timely sensory feedback within less than a second in order to avoid face touching.

Pterygium excision after LASIK.

PURPOSE: To describe the management of a symptomatic pterygium in an eye with previous LASIK surgery. OBSERVATIONS: Significant infiltration of the LASIK flap by the pterygium was noted intraoperatively necessitating the frequent use of a crescent blade. The infiltrative behavior of the pterygium may reflect the inflammatory state after laser refractive surgery. CONCLUSIONS AND IMPORTANCE: Pterygia are highly prevalent, and with the increasing prevalence of LASIK surgery, the coexistence of these 2 conditions is expected to be increasingly more likely. Optimizing the management of this condition can result in a good functional and cosmetic outcome.

Ocular pain response to treatment in dry eye patients.

PURPOSE: Pain is a frequently reported symptom in dry eye disease (DED). We examine the factors associated with ocular pain severity and patient-reported improvement in ocular pain to commonly used dry eye and pain treatments. METHODS: Cross-sectional study of patients presenting for dry eye management. Demographics, ocular and medical history, OSDI, numeric pain scale, pain descriptors, and subjective response to tried eye drop, systemic, and non-pharmacologic treatments were collected. Statistical analysis was performed to identify differential treatment response in patients with various pain levels using the non-parametric test for trend. RESULTS: 144 patients were categorized into 4 groups according to reported pain severity. Increasing pain was significantly associated with younger age, history of refractive surgery, higher OSDI score, and less likelihood of corneal staining. Patients with higher pain intensity were more likely to report a history of fibromyalgia, depression, anxiety, and migraine. Patients with greater pain severity were less responsive to treatment with artificial tears (p < 0.001), lubricating ointment (p = 0.002), steroid eye drops (p = 0.03), cyclosporine 0.05% (p = 0.03), 20% autologous serum tears (p = 0.01), hot compresses (p = 0.04), lid hygiene (p = 0.002) and punctal occlusion (p = 0.03). CONCLUSIONS: Dry eye patients with severe ocular pain often have associated psychological and systemic pain conditions. Treating the underlying DED is beneficial in reducing ocular pain, however the low rate of a satisfactory response highlights the need for further investigation of effective therapies. Cross-sectional studies can provide guidance in the treatment of patients with dry eye-related ocular pain and guide future prospective studies on potentially effective therapies.

The Boston keratoprosthesis in Stevens-Johnson syndrome.

PURPOSE: To evaluate the use of the Boston keratoprosthesis (KPro) in patients with Stevens-Johnson syndrome (SJS). DESIGN: Retrospective, noncomparative, interventional case series. METHODS: Sixteen eyes of 15 patients with SJS underwent KPro surgery at the Massachusetts Eye and Ear Infirmary from January 2000 through December 2005. The preoperative, operative, and postoperative findings were recorded. All patients underwent either the type I or type II Boston KPro surgery by one surgeon (C.H.D.). Retention of the prosthesis, best-corrected visual acuity, the need for surgical revision, and postoperative complications were recorded. The outcomes were compared with those of an earlier group of patients from the 1990s. RESULTS: The mean age of patients was 50+/-18 years (range, 23 to 74 years), and the mean duration of their disease was 10+/-6.6 years. The mean follow-up period was 3.6+/-1.5 years (range, 10.2 months to 5.6 years). Ten eyes underwent type II KPro surgery, whereas six eyes underwent type I KPro surgery. Twelve eyes (75%) achieved a visual acuity of 20/200 or better after surgery, with eight eyes (50%) achieving excellent vision of 20/40 or better. Visual acuity was maintained at 20/200 or better over a mean period of 2.5+/-2.0 years. Preexisting glaucoma was found to be a significant risk factor for visual loss. There were no cases of KPro extrusion or endophthalmitis. CONCLUSIONS: KPro in SJS has improved, largely because of the introduction of vancomycin prophylaxis and better glaucoma treatment. It seems to be superior to standard penetrating keratoplasty, with or without allografted stem cell transplantation, as judged from the literature. However, the outcome of the KPro in SJS is still substantially less favorable than in nonautoimmune diseases.

Keratoprosthesis Decentration and Tilt Results in Degradation in Image Quality.

PURPOSE: To study the effect of decentration and tilt of the type I Boston keratoprosthesis (KPro) on image quality in both aphakic and pseudophakic eyes. METHODS: An optical ray-tracing program was used to simulate the image projected onto the retina in an eye with a perfectly centered KPro, and in eyes with varying degrees of KPro decentration and tilt. Decentration was modeled along a typical white-to-white distance of 12.0 mm, and the corresponding tilt was calculated assuming a radius of curvature of 8.0 mm, the radius of curvature of the backplate of the KPro. Both aphakic and pseudophakic eyes were simulated, and the corresponding modulation transfer function curves, point spread functions, and astigmatism were analyzed. RESULTS: The perfectly centered KPro produced a high-quality image with no induced astigmatism. Increasing decentration beyond approximately 0.5 mm resulted in poorer image quality with a more pronounced effect in the presence of an intraocular lens. Using models of the normal eye as a threshold, image degradation due to decentration becomes clinically significant at approximately 1.4 mm and 0.9 mm for the aphakic and pseudophakic cases, respectively. Astigmatism introduced by decentration is approximately 0.25 D cylinders at those thresholds. CONCLUSIONS: Decentration of up to 0.5 mm had no significant impact on image quality and an attempt at good intraoperative centration of the KPro within this range is important. Conversely, decentration of 0.9 mm or more during surgical implantation can result in significant degradation in retinal image quality including astigmatism. The effect is greater in the pseudophakic eye.

Comparison of EphA receptor tyrosine kinases and ephrinA ligand expression to EphB-ephrinB in vascularized corneas.

PURPOSE: Eph cell surface receptors and their ligands, ephrins, are involved in neuronal patterning and neovascularization. Our purpose is to compare and characterize the expression of ephrinA ligands and EphA receptors to ephrinB ligands and EphB receptors in excised mouse corneal tissue, in corneal epithelial and keratocyte cell lines, and during corneal angiogenesis. METHODS: Mouse corneal epithelial cells and keratocytes were immortalized using SV40T antigen viral infection of primary cultures. The immortalized epithelial cells and keratocytes were cloned and characterized using antibodies to keratin, vimentin, integrin alpha5beta1, and alpha-smooth muscle actin. Basic fibroblast growth factor pellets were implanted to induce corneal neovascularization. The eyes of wild-type, ephrinB2(tlacZ/+), and EphB4(tlacZ/+) heterozygous mice were harvested and sectioned 7 days after pellet implantation. Confocal immunohistochemistry was performed to compare the expression of the Eph/ephrinA family (EphA1-8, ephrinA1-5) and Eph/ephrinB family (EphB1-4, EphB6 ephrinB1-3). RESULTS: EphA1, EphA3, ephrinA1, ephrinA2, EphB1, EphB4, ephrinB1, and ephrinB2 were detected in wild-type mouse corneal epithelial cells and keratocytes. EphA2 was immunolocalized only in epithelial cells. Also, EphA3, ephrinA1, EphB1, EphB4, and ephrinB1 were immunolocalized to the corneal epithelium and stroma. In the vascularized corneas, ephrinB1 was immunolocalized mainly to the keratocytes around the vessels, and ephrinB2, EphB1, and EphB4 were colocalized mainly with CD31 to the vascular endothelial cells. CONCLUSIONS: The characterization of ephrin ligand and Eph receptor expression during cornea angiogensis in this study suggests that the Eph/ephrin family of receptor tyrosine kinases and their ligands may play a role in the regulation of corneal angiogenesis.

Preoperative evaluation of cultured human corneal limbal epithelium on amniotic membrane by confocal microscopy.

PURPOSE: Although sheet transplantation with cultured corneal limbal epithelium has been widely performed as a strategy for ocular surface reconstruction, there has been no optimal method for evaluating the morphology of these sheets prior to transplantation. We propose the use of in vivo confocal microscopy as a novel method for the evaluation of limbal corneal epithelium cultured on amniotic membrane. METHODS: Human limbal epithelial sheets were grown on amniotic membranes by following a standard protocol and were stained with hematoxylin and eosin. Morphology was studied using in vivo confocal microscopy for cultured corneal epithelium on amniotic membrane, human intact amniotic membranes, and epithelium-denuded human amniotic membranes. RESULTS: Histologic examination showed a stratified corneal epithelium sheet by the fourth week of culture. The surface and basal layers of the cultured limbal epithelium and amniotic membrane were clearly distinguished by in vivo confocal microscopy. A monolayer of amniotic epithelial cells was observed on the intact amniotic membrane, but not on the epithelium-denuded human amniotic membrane. CONCLUSIONS: Our findings support the use of in vivo confocal microscopy as a valid technique for the preoperative evaluation of cultured corneal limbal epithelial cell sheets on amniotic membrane.