FL-41 Tint Reduces Activation of Neural Pathways of Photophobia in Patients with Chronic Ocular Pain.

PURPOSE: To assess the therapeutic effect of tinted lenses (FL-41) on photophobia and light-evoked brain activity using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular surface pain. DESIGN: Prospective case series. METHODS: 25 subjects from the Miami veterans affairs (VA) eye clinic were recruited based on the presence of chronic ocular pain, dry eye symptoms, and photophobia. Using a 3T MRI scanner, subjects underwent 2 fMRI scans using an event-related design based on light stimuli: one scan while wearing FL-41 lenses and one without. Unpleasantness ratings evoked by the light stimuli were collected after each scan. RESULTS: With FL-41 lenses, subjects reported decreased (n = 19), maintained (n = 2), or increased (n = 4) light-evoked unpleasantness ratings. Group analysis at baseline (no lens) revealed significant light evoked responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral insula, bilateral frontal pole, visual, precuneus, paracingulate, and anterior cingulate cortices (ACC) as well as cerebellar vermis, bilateral cerebellar hemispheric lobule VI, and bilateral cerebellar crus I and II. With FL-41 lenses, light-evoked responses were significantly decreased in bilateral S1, bilateral S2, bilateral insular, right temporal pole, precuneus, ACC, and paracingulate cortices as well as bilateral cerebellar hemispheric lobule VI. CONCLUSION: FL-41 lenses modulated photophobia symptoms in some individuals with chronic ocular pain. In conjunction, FL-41 lenses decreased activation in cortical areas involved in processing affective and sensory-discriminative dimensions of pain. Further research into these relationships will advance the ability to provide precision therapy for individuals with ocular pain.

Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia.

Introduction: To examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular pain. Methods: Twelve subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: (1) chronic ocular pain; (2) presence of ocular pain over 1 week recall; and (3) presence of photophobia. All individuals underwent an ocular surface examination to capture tear parameters before and 4-6 weeks after BoNT-A injections. Using an event-related fMRI design, subjects were presented with light stimuli during two fMRI scans, once before and 4-6 weeks after BoNT-A injection. Light evoked unpleasantness ratings were reported by subjects after each scan. Whole brain blood oxygen level dependent (BOLD) responses to light stimuli were analyzed. Results: At baseline, all subjects reported unpleasantness with light stimulation (average: 70.8 ± 32.0). Four to six weeks after BoNT-A injection, unpleasantness scores decreased (48.1 ± 33.6), but the change was not significant. On an individual level, 50% of subjects had decreased unpleasantness ratings in response to light stimulation compared to baseline ("responders," n = 6), while 50% had equivalent (n = 3) or increased (n = 3) unpleasantness ("non-responders"). At baseline, several differences were noted between responders and non-responders; responders had higher baseline unpleasantness ratings to light, higher symptoms of depression, and more frequent use of antidepressants and anxiolytics, compared to non-responders. Group analysis at baseline displayed light-evoked BOLD responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, midcingulate cortex (MCC), bilateral frontal pole, bilateral cerebellar hemispheric lobule VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, S2 cortices, cerebellar hemispheric lobule VI, cerebellar crus I, and left cerebellar crus II. BoNT-A responders displayed activation of the spinal trigeminal nucleus at baseline where non-responders did not. Discussion: BoNT-A injections modulate light-evoked activation of pain-related brain systems and photophobia symptoms in some individuals with chronic ocular pain. These effects are associated with decreased activation in areas responsible for processing the sensory-discriminative, affective, dimensions, and motor responses to pain.

Clinical Neuroimaging of Photophobia in Individuals With Chronic Ocular Surface Pain.

PURPOSE: To examine neural mechanisms underlying photophobia in individuals with chronic ocular surface pain by using functional magnetic resonance imaging (fMRI). DESIGN: Cross-sectional case/control analysis. METHODS: A total of 16 individuals from the Miami Veterans Affairs eye clinic underwent comprehensive ocular surface evaluations and were surveyed for ocular surface symptoms. Case patients included patients who reported chronic ocular surface pain symptoms and light sensitivity at least most of the time over 1 week. Controls included persons without chronic ocular surface pain who reported no or minimal light sensitivity. All patients viewed light stimuli during 2 fMRI scans, one before and one after topical anesthetic instillation, and rated their level of pain intensity to the stimulus at the end of each scan. Areas of brain activation in response to light stimuli presentation were correlated with pain responses and examined post- vs pre-anesthesia. RESULTS: Case patients (n = 8) reported higher pain intensity ratings than controls (n = 8) in response to light stimuli during fMRI. Case patient ratings correlated more with light-evoked activation in pain-related areas within the trigeminal brainstem, primary somatosensory cortex (S1), anterior mid-cingulate cortex (aMCC), and insula than in controls. Topical anesthesia led to varying responses in pain ratings among case patients as well as decreased light-evoked activation in S1 and aMCC. CONCLUSIONS: The trigeminal nociceptive system may contribute to photophobia in individuals with chronic ocular surface pain. We demonstrate modulation of cortical structures in this pathway with topically applied anesthetic to the eyes. Further understanding of modulatory interactions that govern ocular surface pain and photophobia is critical for developing effective, precision-based therapies.

Risk Factors for Failure of Tube Shunt Surgery: A Pooled Data Analysis.

PURPOSE: To identify the risk factors associated with failure of tube shunt surgery. DESIGN: Pooled analysis of 3 prospective multicenter, randomized clinical trials. METHODS: A total of 621 patients with medically uncontrolled glaucoma were enrolled, including 276 from the Ahmed Baerveldt Comparison Study, 238 from the Ahmed Versus Baerveldt Study, and 107 from the tube group of the Tube Versus Trabeculectomy Study. Patients were randomized to treatment with an Ahmed glaucoma valve (model FP7) or Baerveldt glaucoma implant (model 101-350). The associations between baseline risk factors and tube shunt failure were assessed using a Cox proportional hazards regression model. The primary outcome measure was the rate of surgical failure defined as intraocular pressure (IOP) > 21 mmHg or reduced < 20% from baseline, IOP ≤ 5 mmHg, loss of light perception vision, reoperation for glaucoma, or removal of implant. RESULTS: The cumulative probability of failure after tube shunt surgery was 38.3% after 5 years. In multivariable analyses, baseline factors that predicted tube shunt failure included preoperative IOP (≤ 21 mmHg compared to IOP > 21 and ≤ 25 mmHg; HR, 2.34; 95% CI, 1.52-3.61; P < .001), neovascular glaucoma (HR, 1.79; 95% CI, 1.28-2.52; P = .001), randomized treatment (for Ahmed glaucoma valve; HR, 1.36; 95% CI, 1.04-1.78; P = .025), and age (for 10 year decrease in age; HR, 1.19; 95% CI, 1.09-1.31; P < .001). CONCLUSIONS: Lower preoperative IOP, neovascular glaucoma, Ahmed implantation, and younger age were predictors of tube shunt failure. This Study provides the largest prospectively collected dataset on tube shunt surgery.

Dry Eye Symptoms and Signs in US Veterans With Gulf War Illness.

PURPOSE: To examine dry eye (DE) symptoms and signs in individuals with vs without Gulf War illness (GWI). DESIGN: Prospective cross-sectional study. METHODS: We performed a prospective, cross-sectional study of South Florida veterans who were active duty during the Gulf War era (GWE; 1990-1991) and seen at an eye clinic between October 1, 2020, and March 13, 2021. Veterans were split into 2 groups: those who met Kansas criteria for GWI (cases, n = 30) and those who did not (controls, n = 41). DE symptoms were assessed via standardized questionnaires whereas DE signs were assessed using a series of ocular surface parameters. Differences between groups were assessed via Mann-Whitney U test. Linear regression analyses were used to examine which GWI symptoms most closely aligned with DE symptoms. RESULTS: Veterans with GWI had higher DE symptoms scores compared to controls (Ocular Surface Disease Index [OSDI] scores: mean 41.20±22.92 vs 27.99±24.03, P = .01). In addition, veterans with GWI had higher eye pain scores compared with controls (average eye pain over past week: 2.63±2.72 vs 1.22±1.50, P = .03), including on neuropathic ocular pain questionnaires (Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 17.33±17.20 vs 9.63±12.64, P = .03). DE signs were mostly similar between the groups. GWI symptoms "nausea or upset stomach" (ß=14.58, SE = 3.02, P < .001) and "headache" (ß=7.90, SE = 2.91, P = .011) correlated with higher OSDI scores. CONCLUSION: Individuals with GWI have more severe DE symptoms and ocular pain scores but similar tear and ocular surface parameters compared to controls without GWI. This finding suggests that mechanisms beyond tear dysfunction drive eye symptoms in GWI.

Perceptions of a Virtual Interview Exercise for Ophthalmology Residency Applicants.

Importance In-person interviews have traditionally been considered a crucial component of the residency application process. Virtual interviews (VIs) became the standard format for the 2020 to 2021 application cycle due to the novel coronavirus disease 2019 (COVID-19) pandemic. VIs offer a new perspective and challenge to this process which warrants unique considerations and further understanding of effects on applicants. Objective This study aimed to assess the perceived efficacy of a VI preparedness exercise for ophthalmology residency applicants in the 2021 residency application cycle. Design, Setting, and Participants A cross-sectional survey was distributed online. All participants in a mock VI exercise conducted via video-telecommunication technology were invited to complete the survey. Data collection occurred from October 12, 2020, to November 2, 2020. A follow-up survey after a match results released was distributed to all participants and data collection occurred from February 18, 2021, to February 25, 2021. Main Outcome and Measures Applicant demographics, comfort, and attitudes toward VIs and VI practice were the primary measurements of this study. Results Responses to the initial survey were received from all 35 participants (100%) in the VI mock interviews. There was a statistically significant difference between the pre- and postinterview responses for "How prepared do you feel for virtual interviews with residency programs?" ( p = 0.0003) and "How likely are you to practice virtual interviews with someone you know?" ( p = 0.0023). Participants reported feeling more prepared for VIs with residency programs after the mock interview ( p = 0.002). A greater proportion of participants responded with "Very Likely" after the mock interview in comparison to before the interview to the questions "How likely are you to practice interviews with someone you know?" ( p = 0.039) and "How likely are you to practice virtual interviews in the same room/area as you will during the official interview season?" ( p = 0.021). Of the 35 original participants, 20 completed the follow-up survey. There were an equal number of participants who responded either "Helped Somewhat" ( n = 9) or "Helped Greatly" ( n = 9) to "How much did the VI mock exercise help you for the actual interview season?" in the follow-up survey. The majority of follow-up survey respondents (17/20) reported that they had additional practice in the virtual environment for interviews after the VI mock exercise. There was no significant difference in perceived helpfulness of the VI mock exercise during the actual interview season between matched and unmatched participants. Conclusion and Relevance As residency applicants prepare for future VIs, practice and adequate preparation will be essential. In this study, implementation of a VI preparedness exercise had a positive impact on applicants' perception of their preparedness and intention to practice the format in the future.

Recent advances on visual cycle protein research and progress on clinical translation.

Since the publication of our previous paper, Visual cycle proteins: Structure, function, and roles in human retinal disease (Tsin, et.al, JBC 293:13016, 2018) there has been significant progress on multiple topics discussed in this paper. In the present communication, we further explore research advances on two visual cycle proteins: DES1 and IRBP. In addition, we emphasize the progress of clinical translation of other visual cycle protein research, including the breakthrough of FDA-approved gene therapy for Leber's congenital amaurosis, and additional gene therapies at different stages of clinical trials for various retinal diseases such as retinitis pigmentosa, diabetic retinopathy, and Stargardt's disease.