The photic blink reflex as an index of photophobia.

Two recent studies of eye closure triggered by intense luminance increase suggest that this behavior reflects the melanopsin-based retinal activity known to underlie photophobia, the pathological aversion to light (Kardon, 2012; Kaiser et al., 2021). Early studies of the photic blink reflex (PBR) are reviewed to help guide future research on this possible objective index of photophobia. Electromyographic recordings of the lid-closure muscle, orbicularis oculi, reveal distinct bursts with typical onset latencies of 50 and 80 ms, R50 and R80, respectively. The latter component appears to be especially sensitive to visual signals from intrinsically photosensitive retinal ganglion cells (ipRGCs) and to prior trigeminal nociceptive stimuli. The authors argue that the R80's function, in addition to protecting the eyeballs from physical contact, is to shape the upper and lower eyelids into a narrow slit to restrict incoming light. This serves to prevent retinal bleaching or injury, while allowing continued visual function.

The relationship between cerebral and retinal microbleeds in cerebral amyloid angiopathy (CAA): A pilot study.

BACKGROUND: The standard in vivo diagnostic imaging technique for cerebral amyloid angiopathy (CAA) is costly and thereby of limited utility for point-of-care diagnosis and monitoring of treatment efficacy. Recent recognition that retinal changes may reflect cerebral changes in neurodegenerative disease provides an ideal opportunity for development of accessible and cost-effective biomarkers for point-of-care use in the detection and monitoring of CAA. In this pilot study, we examined structural and angiographic retinal changes in CAA patients relative to a control group, and compared retinal and cerebral pathology in a group of CAA patients. METHODS: We used spectral domain optical coherence tomography (SD-OCT) to image the retina and compared retinal microbleeds to both cerebral microbleeds and white matter hyperintensities (WMH) in CAA patients, as seen on MRI. We compared retinal angiographic changes, along with structural retinal neuronal layer changes in CAA patients and cognitively normal older adults, and examined the relationship between retinal and cerebral microbleeds and cognition in CAA patients. RESULTS: We found a trend level correlation between retinal and cerebral microbleeds in CAA patients. Moreover, we found a significant correlation between retinal microbleeds and episodic memory performance in CAA patients. There were no significant group differences between CAA patients and cognitively normal older adults on retinal angiographic or structural measurements. CONCLUSION: Retinal microbleeds may reflect degree of cerebral microbleed burden in CAA. This picture was complicated by systolic hypertension in the CAA group, which is a confounding factor for the interpretation of these data. Our results stimulate motivation for pursuit of a more comprehensive prospective study to determine the feasibility of retinal biomarkers in CAA.

Change in retinal structural anatomy during the preclinical stage of Alzheimer's disease.

INTRODUCTION: We conducted a 27-month longitudinal study of mid-life adults with preclinical Alzheimer's disease (AD), using spectral domain optical coherence tomography to compare changes in volume and thickness in all retinal neuronal layers to those of age-matched healthy control subjects. METHODS: Fifty-six older adults (mean age = 65.36 years) with multiple risk factors for AD completed spectral domain optical coherence tomography retinal imaging and cognitive testing at baseline. Twenty-seven months later, they completed the same examinations and an 18F-florbetapir positron emission tomography imaging study. RESULTS: Compared to healthy control subjects, those in the preclinical stage of AD showed a significant decrease in macular retinal nerve fiber layer (mRNFL) volume, over a 27-month follow-up interval period, as well as a decrease in outer nuclear layer and inner plexiform layer volumes and thickness in the inferior quadrant. However, only the mRNFL volume was linearly related to neocortical positron emission tomography amyloid standardized uptake value ratio after controlling for any main effects of age (R2 = 0.103; ρ = 0.017). Furthermore, the magnitude of mRNFL volume reduction was significantly correlated with performance on a task of participants' abilities to efficiently integrate visual and auditory speech information (McGurk effect). DISCUSSION: We observed a decrease in mRNFL, outer nuclear layer, and inner plexiform layer volumes, in preclinical AD relative to controls. Moreover, the largely myelinated axonal loss in the RNFL is related to increased neocortical amyloid-ß accumulation after controlling for age. Volume loss in the RNFL, during the preclinical stage, is not related to performance on measures of episodic memory or problem solving. However, this retinal change does appear to be modestly related to relative decrements in performance on a measure of audiovisual integration efficiency that has been recently advanced as a possible early cognitive marker of mild cognitive impairment.

Increased Prevalence of Optic Disc Drusen after Papilloedema from Idiopathic Intracranial Hypertension: On the Possible Formation of Optic Disc Drusen.

This is a 25-year observational retrospective review of 372 consecutive participants with optic disc drusen or resolved papilloedema from idiopathic intracranial hypertension. The prevalence of optic disc drusen at 19% among eyes with resolved papilloedema was approximately 10 times higher and significantly increased (p < 0.001) as compared with the occurrence in the general population. Eyes with both resolved papilloedema and optic disc drusen had similar visual acuity and visual field outcome as compared with resolved papilloedema alone. Eyes with exposed drusen had significantly worse visual acuity and visual field outcome (p < 0.001) than buried drusen. The high prevalence of optic disc drusen after papilloedema has resolved suggests a non-coincidental relationship. Optic disc drusen formation can be a sequela of papilloedema.

Nonvascular retinal imaging markers of preclinical Alzheimer's disease.

INTRODUCTION: In patients with Alzheimer's disease (AD) and mild cognitive impairment, structural changes in the retina (i.e., reduced thicknesses of the ganglion cell and retinal nerve fiber layers and inclusion bodies that appear to contain beta-amyloid protein [Ab]) have been previously reported. We sought to explore whether anatomic retinal changes are detectable in the preclinical stage of AD. METHODS: A cross-sectional study (as part of an ongoing longitudinal cohort study) involving 63 cognitively normal adults, all of whom have a parent with AD and subjective memory complaints. We compared neocortical amyloid aggregation (florbetapir PET imaging) to retinal spectral domain optical coherence tomography (SD-OCT) markers of possible disease burden. Retinal biomarkers, including the number and surface area of retinal inclusion bodies and the thickness of retinal neuronal layers, were compared across groups with high vs. low neocortical beta-amyloid load. RESULTS: The surface area of inclusion bodies increased as a function of cortical amyloid burden. Additionally, there was a trend toward a selective volume increase in the inner plexiform layer (IPL; a layer rich in cholinergic activity) of the retina in Aß+ relative to Aß- participants, and IPL volume was correlated with the surface area of retinal inclusion bodies. DISCUSSION: These initial results suggest that retinal imaging may be a potential cost-effective and noninvasive technique that can be used to identify those at-risk for AD. Layer-specific changes in the IPL and their association with surface area of inclusion bodies are discussed as a possible reflection of early inflammatory processes associated with cholinergic disruption and concurrent Ab accumulation in the neocortex.

Glaucoma as a Neurodegenerative Disease: Why We Must 'Look for the Protein'.

For years, clinicians and scientists interested in glaucoma have focused on the anterior segment of the eye and lowering of the intraocular pressure with respect to glaucoma causes and therapies. Yet glaucoma progresses in many individuals despite lowering the intraocular pressure. Herein, the concept of glaucoma as a neurodegenerative disease is presented. [Full article available at http://rimed.org/rimedicaljournal-2016-06.asp, free with no login].

Pseudotumor cerebri: What We Have Learned from the Idiopathic Intracranial Hypertension Treatment Trial.

Idiopathic intracranial hypertension, also known as pseudotumor cerebri, is an unexplained increase in intracranial pressure associated with permanent severe visual loss in 25% of cases and debilitating headaches. The condition is often associated with obesity. The Idiopathic Intracranial Hypertension Treatment Trial, a large, randomized, collaborative clinical trial, evaluated the efficacy of acetazolamide with weight loss versus placebo with weight loss in participants. Herein, we describe the major components of the clinical trial and discuss its shortcomings. [Full article available at http://rimed.org/rimedicaljournal-2016-05.asp, free with no login].

Levodopa as a possible treatment of visual loss in nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To determine the clinical effectiveness and potential neuroprotection of levodopa in improving visual acuity, visual field, and retinal nerve fiber layer (RNFL) thickness in eyes affected by NAION. METHOD: Retrospective cohort study involving 59 eyes of 59 participants with NAION who were evaluated within 15 days of NAION onset. Participants received 25 mg carbidopa/100 mg levodopa three times daily with meals for 12 weeks (levodopa group) or were untreated (control group). Best-corrected visual acuity converted to logMAR, mean deviation (MD) threshold sensitivity on automated perimetry, and mean RNFL thickness on optical coherence tomography (OCT) were assessed. The primary outcome was the categorization of eyes into improved visual acuity (by 0.3 logMAR difference), worsened visual acuity (by 0.3 logMAR difference), or no change in visual acuity. The proportions in each category were compared between the levodopa and control groups. RESULTS: Among participants with 20/60 or worse initial visual acuity, levodopa-treated participants had significant improvement (P < 0.0001) in the mean change from initial to final logMAR visual acuity of -0.74 ± 0.56 (95 % CI, -0.98 to -0.50), while the mean change for the control group at -0.37 ± 1.09 (95 % confidence interval estimate, -1.00 to +0.26) was not significant (P = 0.23). A significant difference between groups was observed (P = 0.0086) such that 19/23 (83 %) in the levodopa group improved and none got worse, as compared with 6/14 (43 %) in the control group improving while four (29 %) worsened. The change in visual field MD and RNFL thickness on OCT showed no significant difference at P = 0.23 and P = 0.75 respectively. No levodopa-treated participant had any adverse event from the levodopa. CONCLUSIONS: Treatment within 15 days of onset of NAION with levodopa improved central visual acuity by an average of 6 lines on Snellen acuity chart. Levodopa may promote neuroprotection of the maculopapular retinal ganglion cell fibers in NAION.

Short-term use of inhaled and intranasal corticosteroids is not associated with glaucoma progression on optical coherence tomography.

PURPOSE: To compare the changes in retinal nerve fiber layer (RNFL) thickness and optic nerve cup/disc ratio on optical coherence tomography (OCT) between users and nonusers of inhaled and intranasal corticosteroids (ICS). METHODS: Retrospective study of participants with glaucoma or glaucoma suspect having 2 or more OCTs during a 6-year period. The rates of change in Stratus OCT fast RNFL thickness scan and fast optic disc scan data were compared between ICS users and nonuser controls using random coefficient models. RESULTS: A total of 170 participants met the inclusion criteria, of whom 42 (25%) were ICS users and 128 (75%) were controls. The mean duration of follow-up was 3.2 years. There were no significant differences in the mean rates of change in superior RNFL (-0.8874 µm/y ICS users; -0.8592 µm/y controls; p=0.943), nasal RNFL (-0.0529 µm/y ICS users; -0.3577 µm/y controls; p=0.419), inferior RNFL (0.2703 µm/y ICS users; -0.1910 µm/y controls; p=0.165), and temporal RNFL (-0.3618 µm/y ICS users; -0.3612 µm/y controls; p=0.998) between ICS users and controls. There were no significant differences in the mean rates of change in horizontal cup/disc ratio (-0.0047 µm/y ICS users; 0.0002 µm/y controls; p=0.212) and vertical cup/disc ratio (0.0013 µm/y ICS users; 0.0029 µm/y; p=0.717) between ICS users and controls. CONCLUSIONS: We found no significant difference in the rates of RNFL or optic nerve cup/disc ratio progression among individuals with glaucoma or glaucoma suspect following short-term ICS use.

Amiodarone-associated optic neuropathy: a critical review.

Although amiodarone is the most commonly prescribed anti-arrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone-associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System and published case reports were reviewed. A total of 296 reports were identified: 214 from the Adverse Event Reporting System, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone-associated optic neuropathy (44%) was the most common presentation, and nearly one third were asymptomatic. Optic disk edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (<20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted.

Visual neuropraxia and progressive vision loss from thyroid-associated stretch optic neuropathy.

PURPOSE: Animal models have provided information on the tensile strength of the optic nerve, but to our knowledge no in vivo study of the tensile strength of the human optic nerve has been reported. Accordingly, we present 3 cases of stretch optic neuropathy, an often unrecognized cause of vision loss from thyroid eye disease. METHODS: Observational study of thyroid-associated stretch optic neuropathy. RESULTS: Three cases of stretch optic neuropathy were identified. Visual acuity was better than 20/40. Two patients had arcuate scotoma. Moderate to severe proptosis of 25 to 33 mm was present, without evidence of apical orbital compression. Two patients had retinal hemorrhages suggesting venous stasis retinopathy; the venous stasis retinopathy resolved after orbital decompression. Orbital decompression resulted in improvement of visual function. The rate of decibel sensitivity loss on automated perimetry was estimated at -0.042 dB/da in one case, with complete blindness projected to occur within 785 days from the onset of visual symptoms. CONCLUSIONS: Stretch optic neuropathy presents initially as neuropraxia with temporary visual loss. Orbital decompression should be considered for treatment before permanent and irreversible visual loss ensues.

Differentiating optic disc edema from optic nerve head drusen on optical coherence tomography.

OBJECTIVE: To assess optical coherence tomography in differentiating optic disc edema (ODE) due to papilledema and other optic neuropathies from optic nerve head drusen (ONHD). METHODS: Optical coherence tomographic images from 60 subjects (20 with ODE, 20 with ONHD, and 20 control subjects) were assessed qualitatively and quantitatively. Qualitative criteria for ODE included an elevated optic nerve head with smooth internal contour and subretinal hyporeflective space (SHYPS) with recumbent "lazy V" pattern. Optic nerve head drusen displayed a "lumpy-bumpy" internal optic nerve contour and a rapid decline in SHYPS thickness. Quantitative comparisons included retinal nerve fiber layer and SHYPS thickness. RESULTS: Optical coherence tomography differentiated ODE from ONHD qualitatively (sensitivity, 63%; specificity, 63%) and quantitatively (sensitivity, 80%; specificity, 90%). Respective differences in mean retinal nerve fiber layer thickness between ODE and ONHD were significant (P < .002) superiorly (206.8 vs 121.7 microm), nasally (176.3 vs 78.6 microm), inferiorly (247.2 vs 153.8 microm), and temporally (180.0 vs 85.5 microm). Respective differences in mean SHYPS thickness between ODE and ONHD were significant (P < .001) at radii of 0.75 mm (512.1 vs 274.4 microm), 1.5 mm (291.4 vs 103.0 microm), and 2.0 mm (145.5 vs 60.7 microm). CONCLUSION: Optical coherence tomography can differentiate ODE from ONHD, particularly when the nasal retinal nerve fiber layer and SHYPS thickness at the 2.0-mm radius are greater than 86 microm and 127 microm, respectively.

Closely spaced stressful life events precede the onset of benign essential blepharospasm and hemifacial spasm.

BACKGROUND: The purpose of this study was to assess the possible role of major stressful life events, complicated grief, and depression in the pathogenesis of benign essential blepharospasm (BEB) and hemifacial spasm (HFS). METHODS: This was a case-control study involving 23 participants with BEB/HFS and 23 control subjects, comparing the frequency of major stressful life events, depression on the Beck Depression Inventory-II, and complicated grief on the Inventory of Complicated Grief. RESULTS: There was no difference in the rate of depression or complicated grief between participants with BEB/HFS (57%) and control subjects (48%). Participants with BEB/HFS experienced a significantly (P = 0.0048) shorter time interval between two major stressful life events (median, 0.3 year) than did the control group (median, 3.0 years). The proportion of participants who had suffered two major stressful lifetime events separated by 1 year or less was significantly greater for participants with BEB/HFS than for control subjects (P = 0.0007). CONCLUSIONS: The onset of BEB and HFS was often preceded by a major lifetime stressor. The development of these conditions was significantly related to the number of stressful life events occurring within the preceding year rather than to the total number of stressful life events. Subjects who sustain closely spaced stressful life events may be at increased risk of developing BEB and HFS.

Development and validation of a computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial.

BACKGROUND: The objective of this report is to describe the methods used to develop and validate a computerized system to analyze Humphrey visual fields obtained from patients with non-arteritic anterior ischemic optic neuropathy (NAION) and enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT). The IONDT was a multicenter study that included randomized and non-randomized patients with newly diagnosed NAION in the study eye. At baseline, randomized eyes had visual acuity of 20/64 or worse and non-randomized eyes had visual acuity of better than 20/64 or were associated with patients refusing randomization. Visual fields were measured before treatment using the Humphrey Field Analyzer with the 24-2 program, foveal threshold, and size III stimulus. METHODS: We used visual fields from 189 non-IONDT eyes with NAION to develop the computerized classification system. Six neuro-ophthalmologists ("expert panel") described definitions for visual field patterns defects using 19 visual fields representing a range of pattern defect types. The expert panel then used 120 visual fields, classified using these definitions, to refine the rules, generating revised definitions for 13 visual field pattern defects and 3 levels of severity. These definitions were incorporated into a rule-based computerized classification system run on Excel(R) software. The computerized classification system was used to categorize visual field defects for an additional 95 NAION visual fields, and the expert panel was asked to independently classify the new fields and subsequently whether they agreed with the computer classification. To account for test variability over time, we derived an adjustment factor from the pooled short term fluctuation. We examined change in defects with and without adjustment in visual fields of study participants who demonstrated a visual acuity decrease within 30 days of NAION onset (progressive NAION). RESULTS: Despite an agreed upon set of rules, there was not good agreement among the expert panel when their independent visual classifications were compared. A majority did concur with the computer classification for 91 of 95 visual fields. Remaining classification discrepancies could not be resolved without modifying existing definitions. Without using the adjustment factor, visual fields of 63.6% (14/22) patients with progressive NAION and no central defect, and all (7/7) patients with a paracentral defect, worsened within 30 days of NAION onset. After applying the adjustment factor, the visual fields of the same patients with no initial central defect and 5/7 of the patients with a paracentral defect were seen to worsen. CONCLUSION: The IONDT developed a rule-based computerized system that consistently defines pattern and severity of visual fields of NAION patients for use in a research setting.

Facilitation as well as inhibition of the blink reflex by a visual prepulse requires intact striate cortex.

OBJECTIVE: The role of visual cortex in modulation of the human eye blink reflex was assessed. METHODS: Participants were 13 patients with unilateral striate cortex damage. Nonreflexogenic gratings were presented in their intact or blind hemifield prior to white noise or air puff blink-eliciting stimuli. RESULTS: Inhibition of reflex amplitude was observed at asynchronies ranging from about 120 to 600ms for visible but not invisible prepulses. Facilitation by intact-hemifield gratings was observed for (1) the latency of the acoustic blink reflex, (2) the amplitude of the disynaptic cutaneous blink reflex, R1, and (3) the latency of voluntary hand-grip reactions to the reflexogenic stimuli. These facilitatory effects were absent on trials with blind-hemifield prepulses. CONCLUSIONS: An intact V1 is required for prepulse facilitation as well as inhibition. SIGNIFICANCE: These results extend a popular model of sensorimotor gating deficits in schizophrenia.

Repeated intervals of high-dose corticosteroid: an overlooked therapy in multiple sclerosis.

The rate of conversion to multiple sclerosis is about 6% per year for five years after the first episode of optic neuritis. While the new MS agents have garnered much attention as promising agents to prevent MS relapses, an overlooked therapy is pulse high-dose corticosteroid (10 mg per kg or greater) as an intervention to delay or prevent the development of MS. Data from Optic Neuritis Treatment Trial (ONTT) and other studies underscore the need to investigate the efficacy of high-dose corticosteroid in MS.

The clinical spectrum of amiodarone-associated optic neuropathy.

PURPOSE: To describe the clinical spectrum of amiodarone-associated optic neuropathy. METHODS: Observational cases series and review. RESULTS: Of 55 cases, the median interval for onset of optic neuropathy was four months after initiating amiodarone; 88% occurred within 12 months. Seven (13%) patients were asymptomatic. Twenty-two (40%) patients presented with sudden visual loss, while 26 (47%) had insidious loss of vision. Visual acuity ranged from 20/15 to light perception; 10 (18%) patients had legal blindness with visual acuity of 20/200 or worse. Visual field loss was present in 91% of cases. Color vision loss was present in eight (40%) of 20 cases. Optic disc edema was present in 85% of cases, while eight (15%) patients had retrobulbar optic neuropathy, without evidence of disc edema. Optic disc edema resolved over a median time of three months. Five patients had raised intracranial pressure on lumbar puncture. CONCLUSION: We were able to classify amiodarone-associated optic neuropathy into five clinical categories with respect to temporal characteristics and optic nerve appearance: insidious-onset (43%), acute-onset (28%), retrobulbar (13%), increased intracranial pressure (8%), and delayed-progressive onset (8%). Most cases of optic neuropathy commenced within 12 months of initiating amiodarone, with the median onset being four months. Over 10% of patients will have no visual symptoms at the onset. Ophthalmologic examinations within the first 12 months--and particularly within four months of initiating amiodarone--should improve early detection of amiodarone-associated optic neuropathy.