Pseudovitelliform maculopathy associated with deferoxamine toxicity: multimodal imaging and electrophysiology of a rare entity.

Deferoxamine is a commonly used chelating agent for secondary hemochromatosis. We report a rare retinal manifestation of deferoxamine toxicity in a 68-year-old man and provide supporting multimodal imaging and electrophysiology. The patient had iron overload related to transfusion-dependent myelodysplastic syndrome and developed a pseudovitelliform macular lesion related to deferoxamine toxicity. We also describe for the first time the worsening of this maculopathy on deferasirox, an alternative chelating agent. Macular pseudovitelliform lesion is a unique manifestation of deferoxamine toxicity that can be mistaken for pattern dystrophy. It is important to recognize this manifestation, because discontinuation of the offending agent may halt or reverse the toxicity.

Leptin modulates nutrient reward via inhibitory galanin action on orexin neurons.

OBJECTIVE: Leptin modulates food reward via central leptin receptor (LepRb) expressing neurons. Food reward requires stimulation of midbrain dopamine neurons and is modulated by central leptin action, but the exact central mechanisms remain unclear. Stimulatory and inhibitory leptin actions on dopamine neurons have been reported, e.g. by indirect actions on orexin neurons or via direct innervation of dopamine neurons in the ventral tegmental area. METHODS: We showed earlier that LepRb neurons in the lateral hypothalamus (LHA) co-express the inhibitory acting neuropeptide galanin (GAL-LepRb neurons). We studied the involvement of GAL-LepRb neurons to regulate nutrient reward in mice with selective LepRb deletion from galanin neurons (GAL-LepRb(KO) mice). RESULTS: We found that the rewarding value and preference for sucrose over fat was increased in GAL-LepRb(KO) mice compared to controls. LHA GAL-LepRb neurons innervate orexin neurons, but not the VTA. Further, expression of galanin and its receptor GalR1 are decreased in the LHA of GAL-LepRb(KO) mice, resulting in increased activation of orexin neurons. CONCLUSION: We suggest galanin as an important mediator of leptin action to modulate nutrient reward by inhibiting orexin neurons.

Cyclotorsional and non-cyclotorsional components of eye rotation observed from sitting to supine position.

PURPOSE: Evaluate average cyclotorsional and non-cyclotorsional components (NCY) of eye rotation from sitting to supine, and associate average cyclotorsion to different variables. METHODS: Medical records of patients who underwent bilateral sequential laser refractive surgery were retrospectively evaluated. Recorded variables included the patient's age, refraction, automated keratometry, pupil displacement and eye rotation from sitting to supine position. Measured iris rotation (total rotation, TR) was decomposed into two components: NCY, defined as the common rotation component of each eye of the same patient, and cyclotorsional component (CY), defined as the assumed independent eye rotation for each eye in relation to the face, so that TR=NCY+CY. Cyclotorsion ratio (CR) was calculated as CR=|CY|/|TR|, and used to correlate CY with TR for each eye. RESULTS: Data from 310 eyes of 155 patients were evaluated. TR was +1.43° ±3.41° (-8.30° to +9.20°). Average CYs and NCYs per patient were +1.43°±2.04° (-3.15± to +7.40°) and -0.28°±2.72° (-6.85° to +7.15°), respectively. TR demonstrated that 40.6% and 8.4% of patients presented bilateral excyclotorsion and incyclotorsion, respectively. When excluding NCYs, average CYs demonstrated that 74.2% of patients presented excyclotorsion and 23.9% presented incyclotorsion. CR demonstrated that TR represented from 75% to 125% of average CY in 19.68% of the eyes. TR overestimated and underestimated average CYs above these limits in 52.26% and 28.06% of the eyes, respectively. There was no statistical association between average CYs and the different variables. DISCUSSION: This study demonstrates that most of the rotations previously attributed to torsional components were probably due to NCYs, such as postural misalignments. Apparently, the amplitude of cyclotorsional movements is smaller than observed in previous reports, and could not be associated with any studied variable.

Treatment of recalcitrant radiation maculopathy using intravitreal dexamethasone (Ozurdex) implant.

PURPOSE: Radiation maculopathy is the most common cause of severe vision loss after radiotherapy of uveal melanoma. To date, no effective therapy exists. The authors report a novel approach to the treatment of radiation maculopathy using dexamethasone (Ozurdex, Allergan Inc) intravitreal implant. METHODS: This is a retrospective case series of two patients who developed radiation maculopathy after radiotherapy for uveal melanoma and was treated with Ozurdex. Clinical outcomes included visual acuity, central foveal thickness by optical coherence tomography, intraocular pressure, and cataract formation. RESULTS: Both patients were of Caucasian descent. Patient 1 received charged-particle radiation, whereas Patient 2 received iodine-125 brachytherapy for medium-sized uveal melanoma located in the midperipheral retina. Radiation maculopathy developed 47 months and 18 months after radiation exposure in Patient 1 and 2, respectively. Both patients initially received bevacizumab monotherapy followed by alternating therapy with bevacizumab and intravitreal triamcinolone. Secondary to a limited response, the patients were treated with Ozurdex implants. One patient had visual improvement, and both patients experienced a prolonged time frame of anatomical stability. Adverse effects included a rise in the intraocular pressure, which was controlled by topical hypotensive agents and posterior subcapsular cataract formation in Patient 1. CONCLUSION: Ozurdex intravitreal implant provides a prolonged period of anatomical stabilization in recalcitrant cases of radiation maculopathy in patients who have failed multiple intravitreal bevacizumab injections and had only a partial response to intravitreal triamcinolone. Larger prospective studies are required to determine the extent of visual benefit.

Directed conjunctival biopsy and impact of histologic sectioning methodology on the diagnosis of ocular sarcoidosis.

BACKGROUND: Sarcoidosis is an idiopathic, multi-system, granulomatous disease with well-described ocular manifestations. However, other uveitic etiologies can manifest in a similar fashion, and ocular disease may precede systemic manifestations. Definitive diagnosis requires histologic confirmation of non-caseating granulomatous inflammation. This study reports the diagnostic yield of directed biopsy of conjunctival follicles in patients with uveitis suspected to be secondary to sarcoidosis, and compares an institutional standard tissue sectioning method to a multi-plane technique. RESULTS: A retrospective analysis was performed of all patients who underwent directed conjunctival biopsy for suspected ocular sarcoidosis. A total of eight patients were identified; all were females. Directed conjunctival biopsy was positive in three of seven patients using standard histologic processing method, a yield of 43%. Using the multi-plane technique increased the cumulative yield to 63%. CONCLUSIONS: Directed conjunctival biopsy is a minimally invasive, cost-effective, and moderately high yield method of diagnosing ocular sarcoidosis. Using a multi-plane sectioning method may increase biopsy yield when standard sectioning techniques are negative.

Effect of hemodialysis on intraocular pressure and ocular perfusion pressure.

IMPORTANCE: Elevated intraocular pressure (IOP) and decreased ocular perfusion pressure (OPP) are risk factors for glaucoma development and progression. Unrecognized significant IOP elevation or OPP reduction during hemodialysis (HD) could lead to glaucomatous optic nerve damage and subsequent visual loss. OBJECTIVE: To evaluate changes in IOP and OPP during HD. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional observational study was conducted in patients undergoing HD at an ambulatory care clinic at the University of Illinois at Chicago. EXPOSURES: Forty-nine patients (97 eyes) undergoing HD were enrolled. Exclusion criteria included preexisting corneal abnormalities, history of corneal surgery, allergy to topical anesthetic agents, and current eye infection. Nine patients had previous diagnoses of open-angle glaucoma (OAG) or suspected glaucoma. At 3 time points, IOP was measured using a pneumatonometer and blood pressure was recorded. Measurements were made with the patient in a seated position approximately 15 minutes before starting HD (T1), approximately 2 hours after starting HD (T2), and approximately 15 minutes after ending HD (T3). Mean arterial pressure (MAP) and OPP (systolic, diastolic, and mean OPP) were calculated. MAIN OUTCOMES AND MEASURES: Intraocular pressure and OPP. RESULTS: From T1 to T3, IOP significantly increased by 3.1 mm Hg (both eyes, P < .001), MAP significantly decreased by 5.8 mm Hg (P = .05), and all OPP measures significantly decreased from baseline (all P ≤ .02). Using previously reported thresholds of increased glaucoma development and progression risk, 53% of the right eyes (26 of 49) and 46% of the left eyes (22 of 48) had a systolic OPP of 101 mm Hg or less, 71% of the right eyes (35 of 49) and 73% of the left eyes (35 of 48) had a diastolic OPP of 55 mm Hg or less, and 63% of the right eyes (31 of 49) and 65% of the left eyes (31 of 48) had a mean OPP of 42 mm Hg or less. CONCLUSIONS AND RELEVANCE: Significantly increased IOP and decreased OPP occur during HD, bringing both to levels that increase the risk of glaucoma development and progression. Clinicians should consider HD history in patients who have glaucoma progression, even when IOP has been well controlled. Such patients may benefit from IOP and blood pressure monitoring during HD sessions to minimize OPP changes resulting from IOP spikes and/or suboptimal blood pressure.

Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action.

Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions. LepRb neurons are found throughout the brain, and several distinct populations contribute to energy homeostasis control. However, the function of most LepRb populations remains unknown, and their contribution to regulate energy homeostasis has not been studied. Galanin has been hypothesized to interact with the leptin signaling system, but literature investigating colocalization of LepRb and galanin has been inconsistent, which is likely due to technical difficulties to visualize both. We used reporter mice with green fluorescent protein expression from the galanin locus to recapitulate the colocalization of galanin and leptin-induced p-STAT3 as a marker for LepRb expression. Here, we report the existence of two populations of galanin-expressing LepRb neurons (Gal-LepRb neurons): in the hypothalamus overspanning the perifornical area and adjacent dorsomedial and lateral hypothalamus [collectively named extended perifornical area (exPFA)] and in the brainstem (nucleus of the solitary tract). Surprisingly, despite the known orexigenic galanin action, leptin induces galanin mRNA expression and stimulates LepRb neurons in the exPFA, thus conflicting with the expected anorexigenic leptin action. However, we confirmed that intra-exPFA leptin injections were indeed sufficient to mediate anorexic responses. Interestingly, LepRb and galanin-expressing neurons are distinct from orexin or melanin-concentrating hormone (MCH)-expressing neurons, but exPFA galanin neurons colocalized with the anorexigenic neuropeptides neurotensin and cocaine- and amphetamine-regulated transcript (CART). Based on galanin's known inhibitory function, we speculate that in exPFA Gal-LepRb neurons galanin acts inhibitory rather than orexigenic.

Multifocal retinal astrocytic hamartomas: a case series and review of the literature.

PURPOSE: Retinal astrocytic hamartoma is a benign glial tumor found in the nerve fiber layer, and it is most commonly reported as a solitary lesion. Multiple or bilateral lesions may be indicative of systemic disease, such as tuberous sclerosis complex or neurofibromatosis 1. We present three unique cases of multifocal and bilateral retinal astrocytic hamartomas in patients with suspected tuberous sclerosis complex. The typical features, diagnosis, management, and systemic implications of these retinal lesions are discussed. METHODS: Consecutive case series at a university-based ophthalmology clinic. RESULTS: The age of the patients ranged from 9 years to 27 years. The patients came from different ethnic backgrounds and had no known family history of tuberous sclerosis complex or neurofibromatosis. Two of the three patients had asthma, along with brain and kidney tumors. Two of the three patients had a seizure disorder, and one of the three patients had mental retardation. Only one patient presented with an ocular complaint of decreased vision, as a result of a presumed unrelated process. All patients had bilateral and multifocal astrocytic hamartomas. CONCLUSION: Multifocal retinal astrocytic hamartomas are unique and can be the first manifestation of a systemic disease such as tuberous sclerosis complex or neurofibromatosis 1. Prompt referral for imaging and workup with the appropriate medical subspecialty can help prevent or delay the morbidity related to these systemic conditions.

De novo malignant optic chiasm glioma with initial clinical response to steroids.

Malignant optic nerve glioma (MONG) is a rare but uniformly fatal disease that remains poorly understood. We describe a notable case of this rare disease occurring in the optic chiasm. Normal brain imaging and normal ophthalmic examination two years prior to diagnosis provide evidence for de novo genesis of MONG in our patient. Early response to steroids highlights the degree to which MONG can initially mimic inflammatory optic neuropathies and chiasmal syndromes. Our case also demonstrates a poor outcome with MONG even with current advanced therapy for glioblastoma including radiotherapy plus concomitant and adjuvant temozolomide (the EORTC/NCIC regimen) and bevacizumab.

Skin problems in individuals with lower-limb loss: literature review and proposed classification system.

Problems with skin integrity can disrupt daily prosthesis use and lead to decreased mobility and function in individuals with lower-limb loss. This study reviewed the literature to examine how skin problems are defined and diagnosed and to identify the prevalence and types of skin problems in individuals with lower-limb loss. We searched the literature for terms related to amputation and skin problems. We identified 777 articles. Of the articles, 90 met criteria for review of research methodology. Four clinical studies met our selection criteria. The prevalence rate of skin problems was 15% to 41%. The most commonly reported skin problems were wounds, abscesses, and blisters. Given the lack of standardized definitions of skin problems on residual limbs, we conclude this article with a system for classification.