FLUORESCE: A Pilot Randomized Clinical Trial of Fluoxetine for Vision Recovery After Acute Ischemic Stroke.

BACKGROUND: Poststroke homonymous hemianopia is disabling, and complete spontaneous recovery is rare. In this randomized, placebo-controlled, double-blind, pilot clinical trial, we tested whether fluoxetine enhances vision recovery after stroke. METHODS: We randomized 17 consecutive adults 1:1 to 90 days of fluoxetine 20 mg daily vs placebo within 10 days of an ischemic stroke causing isolated homonymous hemianopia. The primary end point was percent improvement in 24-2 automated perimetry at 6 months. Twelve participants completed the study. Clinical trial registration NCT02737930. RESULTS: Intention-to-treat analysis of the primary end point, percent improvement in perimetric mean deviation, showed a nonsignificant benefit of fluoxetine (64.4%, n = 5) compared with placebo (26.0%, n = 7, one-tailed 95% confidence interval (CI) = (-2.13, ∞), P = 0.06). The original blind field completely recovered in 60% receiving fluoxetine and 14% receiving placebo (odds ratio = 7.22, one-tailed 95% CI = (0.50, ∞)). CONCLUSION: These results suggest a trend in favor of fluoxetine for vision recovery after stroke and have the potential to inform the design of a larger multicenter trial.

Empty Sella Syndrome as a Window Into the Neuroprotective Effects of Prolactin.

Background: The goal of this study was to relate diffusion MR measures of white matter integrity of the retinofugal visual pathway with prolactin levels in a patient with downward herniation of the optic chiasm secondary to medical treatment of a prolactinoma. Methods: A 36-year-old woman with a prolactinoma presented with progressive bilateral visual field defects 9 years after initial diagnosis and medical treatment. She was diagnosed with empty-sella syndrome and instructed to stop cabergoline. Hormone testing was conducted in tandem with routine clinical evaluations over 1 year and the patient was followed with diffusion magnetic resonance imaging (dMRI), optical coherence tomography (OCT), and automated perimetry at three time points. Five healthy controls underwent a complementary battery of clinical and neuroimaging tests at a single time point. Results: Shortly after discontinuing cabergoline, diffusion metrics in the optic tracts were within the range of values observed in healthy controls. However, following a brief period where the patient resumed cabergoline (of her own volition), there was a decrease in serum prolactin with a corresponding decrease in visual ability and increase in radial diffusivity (p < 0.001). Those measures again returned to their baseline ranges after discontinuing cabergoline a second time. Conclusions: These results demonstrate the sensitivity of dMRI to detect rapid and functionally significant microstructural changes in white matter tracts secondary to alterations in serum prolactin levels. The inverse relations between prolactin and measures of white matter integrity and visual function are consistent with the hypothesis that prolactin can play a neuroprotective role in the injured nervous system.

Nonabsorbable intrasellar stent placement for recurrent Rathke cleft cyst: illustrative case.

BACKGROUND: Rathke cleft cyst (RCC) has a recurrence rate of 10% to 22%, and preventing recurrence is challenging. For patients who experience persistent recurrence of RCC, placement of steroid-eluting bioabsorbable intrasellar stents has been rarely described. However, recurrences are often delayed, suggesting that dissolvable stents may not be successful long-term. The release of steroids in close proximity to the pituitary gland may also unintentionally influence the hypothalamic-adrenal-pituitary axis. OBSERVATIONS: The authors present a case of a 66-year-old woman with a persistently recurrent RCC who underwent drainage of her cyst with placement of a nonabsorbable intrasellar stent in the form of a tympanostomy tube. After repeat transsphenoidal drainage of her cyst, a tympanostomy T-tube was placed to stent open the dural aperture. Postoperatively, the patient's condition showed improvement clinically and radiographically. LESSONS: Placement of an intrasellar stent for recurrent RCC has rarely been described. Steroid-eluting bioabsorbable stents may dissolve before RCC recurrence and may have an unintentional effect on the hypothalamic-pituitary-adrenal axis. The authors present the first case of nonabsorbable stent placement in the form of a tympanostomy tube for recurrence of RCC. Additional studies and longer follow-up are necessary to evaluate the long-term efficacy of both absorbable and nonabsorbable stent placement.

Selective serotonin reuptake inhibitors for functional recovery after stroke: similarities with the critical period and the role of experience-dependent plasticity.

There has been a growing interest in the potential for plasticity-inducing pharmacological interventions to enhance post-stroke recovery. One group of drugs that continues to garner a great deal of attention in this regard is a class of antidepressants called the selective serotonin reuptake inhibitors. Here we propose a model for the mechanism by which these drugs may enhance plasticity after ischemic brain injury. First, we review the research in animal models demonstrating how selective serotonin reuptake inhibitors reopen the critical period for ocular dominance plasticity in adulthood. We then compare this period of heightened plasticity to the cellular and biochemical milieu of perilesional tissue after an ischemic event in the adult brain. We argue that selective serotonin reuptake inhibitors administered acutely after an ischemic stroke alter excitatory-inhibitory balance in perilesional tissue and reinstate a type of plasticity reminiscent of the critical period in development. Finally, we discuss opportunities for future research in this area in both the preclinical and clinical realms.

Presentation and Progression of Papilledema in Cerebral Venous Sinus Thrombosis.

PURPOSE: To determine the natural history and visual outcomes of papilledema in cerebral venous sinus thrombosis (CVST). DESIGN: Retrospective observational case series. METHODS: This multicenter study included 7 tertiary care neuro-ophthalmology clinics. Sixty-five patients with CVST were identified who received serial eye examinations with documented papilledema from 2008-2016. Outcome measures included time from diagnosis to papilledema documentation, papilledema progression, time to papilledema resolution, treatment interventions and final visual outcomes. RESULTS: Papilledema was present on initial presentation in 54% of patients or detected later during the course of the disease in 46% of patients. The average time from CVST diagnosis to papilledema documentation was 29 days with a mean (SD) initial Frisén grade of 2.7 (1.3). In 21.5% of cases, papilledema progressed over an average of 55.6 (56.6) days. Time to papilledema resolution was approximately 6 months. Final visual acuity ranged from 20/20 to light perception, with 40% of patients having residual visual field defects on standard automated perimetry. Frisén grade ≥3 (odds ratio [OR] 10.21, P < .0053) and cases with worsening papilledema (3.5, P < .043) were associated with permanent visual field deficits. CONCLUSIONS: Our study indicates the importance of serial ophthalmic evaluation in all cases of CVST. Follow-up fundoscopy is critical given that a subset of cases can show delayed onset and/or worsening of papilledema with time. Specifically, we recommend an ophthalmic examination at the time of initial diagnosis, with repeat examination within a few weeks and further follow-up depending on the level of papilledema or vision changes.

Survival of retinal ganglion cells after damage to the occipital lobe in humans is activity dependent.

Damage to the optic radiations or primary visual cortex leads to blindness in all or part of the contralesional visual field. Such damage disconnects the retina from its downstream targets and, over time, leads to trans-synaptic retrograde degeneration of retinal ganglion cells. To date, visual ability is the only predictor of retinal ganglion cell degeneration that has been investigated after geniculostriate damage. Given prior findings that some patients have preserved visual cortex activity for stimuli presented in their blind field, we tested whether that activity explains variability in retinal ganglion cell degeneration over and above visual ability. We prospectively studied 15 patients (four females, mean age = 63.7 years) with homonymous visual field defects secondary to stroke, 10 of whom were tested within the first two months after stroke. Each patient completed automated Humphrey visual field testing, retinotopic mapping with functional magnetic resonance imaging, and spectral-domain optical coherence tomography of the macula. There was a positive relation between ganglion cell complex (GCC) thickness in the blind field and early visual cortex activity for stimuli presented in the blind field. Furthermore, residual visual cortex activity for stimuli presented in the blind field soon after the stroke predicted the degree of retinal GCC thinning six months later. These findings indicate that retinal ganglion cell survival after ischaemic damage to the geniculostriate pathway is activity dependent.

Using Vision to Study Poststroke Recovery and Test Hypotheses About Neurorehabilitation.

Approximately one-third of stroke patients suffer visual field impairment as a result of their strokes. However, studies using the visual pathway as a paradigm for studying poststroke recovery are limited. In this article, we propose that the visual pathway has many features that make it an excellent model system for studying poststroke neuroplasticity and assessing the efficacy of therapeutic interventions. First, the functional anatomy of the visual pathway is well characterized, which makes it well suited for functional neuroimaging studies of poststroke recovery. Second, there are multiple highly standardized and clinically available diagnostic tools and outcome measures that can be used to assess visual function in stroke patients. Finally, as a sensory modality, the assessment of vision is arguably less likely to be affected by confounding factors such as functional compensation and patient motivation. Given these advantages, and the general similarities between poststroke visual field recovery and recovery in other functional domains, future neurorehabilitation studies should consider using the visual pathway to better understand the physiology of neurorecovery and test potential therapeutics.

Retrospective, Multicenter Comparison of the Clinical Presentation of Patients Presenting With Diplopia From Giant Cell Arteritis vs Other Causes.

BACKGROUND: Although giant cell arteritis (GCA) is a well-known cause of transient and permanent vision loss, diplopia as a presenting symptom of this condition is uncommon. We compared symptoms and signs of patients presenting with diplopia from GCA to those from other causes. METHODS: This was a multicenter, retrospective study comparing the clinical characteristics of patients presenting with diplopia from GCA with age-matched controls. Demographic information, review of symptoms, ophthalmic examination, and laboratory data of biopsy-proven patients with GCA were compared with those of age-matched controls presenting with diplopia. RESULTS: A total of 27 patients presented with diplopia from GCA, 19 with constant diplopia, and 8 with transient diplopia. All patients with constant diplopia from GCA were matched with 67 control subjects who had diplopia from other etiologies. Patients with GCA were more likely to describe other accompanying visual symptoms (58% vs 25%, P = 0.008), a greater number of systemic GCA symptoms (3.5, GCA vs 0.6, controls, P < 0.001) such as headache (94% [17/18] vs 39% [23/67]; P < 0.001), jaw claudication (80% [12/15] vs 0% [0/36]; P < 0.001), and scalp tenderness (44% [7/16] vs 7% [3/43]; P < 0.001). Ocular ischemic lesions (26% vs 1%, P < 0.001) were also common in patients with diplopia from GCA. Inflammatory markers were elevated significantly in patients with GCA vs controls (erythrocyte sedimentation rate: 91% [10/11] vs 12% [3/25], P < 0.001; C-reactive protein: 89% [8/9] vs 11% [2/19], P < 0.001). CONCLUSIONS: GCA is a rare but serious cause of diplopia among older adults and must be differentiated from other more common benign etiologies. Our study suggests that most patients with diplopia from GCA have concerning systemic symptoms and/or elevated inflammatory markers that should trigger further work-up. Moreover, careful ophthalmoscopic examination should be performed to look for presence of ocular ischemic lesions in older patients presenting with acute diplopia.

Spontaneous in-flight accommodation of hand orientation to unseen grasp targets: A case of action blindsight.

The division of labour between the dorsal and ventral visual pathways is well established. The ventral stream supports object identification, while the dorsal stream supports online processing of visual information in the service of visually guided actions. Here, we report a case of an individual with a right inferior quadrantanopia who exhibited accurate spontaneous rotation of his wrist when grasping a target object in his blind visual field. His accurate wrist orientation was observed despite the fact that he exhibited no sensitivity to the orientation of the handle in a perceptual matching task. These findings indicate that non-geniculostriate visual pathways process basic volumetric information relevant to grasping, and reinforce the observation that phenomenal awareness is not necessary for an object's volumetric properties to influence visuomotor performance.

In Vivo Adaptive Optics Ophthalmoscopy Correlated with Histopathologic Results in Cancer-Associated Retinopathy.

PURPOSE: To demonstrate the validity of adaptive optics scanning laser ophthalmoscopy (AOSLO) imaging of the retina in human disease based on clinicopathologic correlation in a patient with cancer-associated retinopathy (CAR). DESIGN: Case report. PARTICIPANT: Sixty-four-year-old man with CAR. METHODS: Fundus photography, electroretinography, visual field testing, fundus autofluorescent imaging, spectral-domain OCT scans, AOSLO, and histopathologic analysis were performed. MAIN OUTCOME MEASURE: Comparison of AOSLO with histopathologic results. RESULTS: Changes in photoreceptor morphologic features were correlated highly between AOSLO and histopathologic results. CONCLUSIONS: We present a unique case where a patient with a rare and fatal disease, CAR, underwent AOSLO imaging during the course of the disease, and then shortly thereafter, postmortem histopathologic analysis of the eyes was carried out. This is the first report of use of AOSLO to elucidate further the retinal changes that occur in CAR and the first study to demonstrate correlation of AOSLO with histopathologic results in any human disease.

Central Retinal Artery Occlusion With Subsequent Central Retinal Vein Occlusion in Biopsy-Proven Giant Cell Arteritis.

Central retinal artery occlusion with subsequent central retinal vein occlusion in the same eye is a rare entity. We present a 72-year-old man with biopsy-proven giant cell arteritis who developed bilateral arteritic anterior ischemic optic neuropathy and a left central retinal artery occlusion. Subsequently, he developed a left central retinal vein occlusion within 2 weeks of his initial vision loss. His vision did not improve with corticosteroids.

White matter changes linked to visual recovery after nerve decompression.

The relationship between the integrity of white matter tracts and cortical function in the human brain remains poorly understood. We investigate reversible white matter injury, in this case patients with compression of the optic chiasm by pituitary gland tumors, to study the structural and functional changes that attend spontaneous recovery of cortical function and visual abilities after surgical removal of the tumor and subsequent decompression of the nerves. We show that compression of the optic chiasm led to demyelination of the optic tracts, which reversed as quickly as 4 weeks after nerve decompression. Furthermore, variability across patients in the severity of demyelination in the optic tracts predicted visual ability and functional activity in early cortical visual areas. Preoperative measurements of myelination in the optic tracts predicted the magnitude of visual recovery after surgery. These data indicate that rapid regeneration of myelin in the human brain is a component of the normalization of cortical activity, and ultimately the recovery of sensory and cognitive function, after nerve decompression. More generally, our findings demonstrate the use of diffusion tensor imaging as an in vivo measure of myelination in the human brain.

Late onset optic neuropathy in methylmalonic and propionic acidemia.

PURPOSE: To describe 3 cases of late-onset bilateral optic neuropathy with visual dysfunction in patients with organic acidemia. DESIGN: Retrospective case series. METHODS: A total of 3 subjects, a 16-year-old male with methylmalonic acidemia (MMA), a 21-year-old male with MMA, and a 20-year-old female with propionic acidemia (PA), are included in this series. Comparison of the patients' clinical course, ophthalmologic exam, and testing are discussed. The outcome measures include visual acuity (VA), fundus appearance, visual fields, brain imaging, and genetic testing. RESULTS: All 3 subjects had late-onset severe bilateral VA loss with bilateral optic nerve pallor, central or cecocentral scotomas on visual field testing, and negative diagnostic workups for other causes of bilateral optic neuropathy. CONCLUSIONS: Patients with organic acidemia may develop late-onset bilateral optic neuropathy with visual dysfunction despite lifelong propiogenic amino acid restriction and dietary supplementation.

Management of exposure keratopathy associated with severe craniofacial trauma.

We describe a case of severe craniofacial trauma with resultant exposure keratopathy that was refractive to traditional treatment measures including aggressive lubrication, tarsorrhaphy, platinum lid weight implantation, punctal plugs, correction of lid retraction, amniotic membrane application, and multiple bandage contact lenses. Through combined Boston scleral lens placement and traumatic cataract extraction with intraocular lens (IOL) implantation using scleral lens IOL power calculations, we were able to maximize patient comfort and attain superior visual acuity. To our knowledge, calculation of IOL power through a scleral lens has not been described.