Cerebrolysin attenuates hyperalgesia, photophobia, and neuroinflammation in a nitroglycerin-induced migraine model in rats.

Chronic migraine dramatically affects the quality of life in the migraineurs. This study examined the effect of chronic cerebrolysin (CBL) treatment on the migraine-associated symptoms in a rat model of migraine. Experiments were carried out on 8 weeks, male Wistar rats. Chronic migraine was modeled by injection (10 mg/kg, i.p) of nitroglycerin (NTG) on days 3, 5, 7, and 9. CBL (2.5 and 5 ml/kg, i.p.) was injected every day for 10 days. Mechanical and thermal withdrawal thresholds of the hind paw were examined by von Frey hairs and hot plate, respectively. Head grooming behavior was evaluated one hour following injection of NTG. Light-aversive behaviors were determined in the modified elevated plus-maze (EPM) on even days and in the light/dark box on odd days. After behavioral experiments, blood concentrations of calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), tumor necrosis factor-a (TNF-α), and interleukin-1ß (IL-1ß) were assessed by rat specific enzyme-linked immunosorbent assay (ELISA) kits. Our results indicated that NTG significantly increased migraine-related behavioral and molecular symptoms in the animals, whereas CBL treatment markedly reduced mechanical and thermal hyperalgesia, head grooming, and light-aversive behaviors induced by NTG. Also, blood levels of CGRP, PACAP, and pro-inflammatory cytokines (TNF-α and IL-1ß) significantly decreased by CBL administration. Chronic CBL treatment showed antinociceptive and light-aversive reducing effects in the NTG-induced animal model of chronic migraine and may represent a valuable therapy for those suffering from migraine.

Chronic ghrelin treatment reduced photophobia and anxiety-like behaviors in nitroglycerin- induced migraine: role of pituitary adenylate cyclase-activating polypeptide.

Chronic migraine is a debilitating disorder that has a significant impact on patients and society. Nearly all migraineurs frequently reported light sensitivity during a headache attack. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the activation of trigeminal system and migraine pain. To identify the effect of chronic ghrelin treatment on endogenous PACAP and associated symptoms of migraine, an experimental chronic migraine model was induced by intermittent intraperitoneal (i.p) injection of nitroglycerin (NTG). Photophobia and anxiety-like behaviors were determined in the modified elevated plus maze on days 2, 4, 6, 8, and 10 and in the light/dark box on days 3, 5, 7, 9, and 11. Blood levels of PACAP and cortisol were assessed by enzyme-linked immunosorbent (ELISA) kits. Chronic injection of NTG evoked photophobia and anxiety-like behaviors and treatment with ghrelin (150 µg/kg) for 11 days effectively attenuated photophobia and anxiety-like behaviors in the both paradigms. We further found that NTG increased the blood levels of PACAP and cortisol, which was significantly reduced by ghrelin treatment. Additionally, staining with Hematoxylin and Eosin (H&E) revealed that ghrelin reduced NTG-induced increase in the number of satellite glial cells in the trigeminal ganglion. Furthermore, for the first time we showed that repeated administrations of NTG increased white blood cell (WBC) counts and mean platelet volume (MPV), and decreased platelet counts. These results indicated that ghrelin decreased migraine associated symptoms possibly through attenuating endogenous PACAP and cortisol levels. Therefore, ghrelin may hold therapeutic potentialities in managing the chronic migraine.

Primary cicatricial alopecia: Other lymphocytic primary cicatricial alopecias and neutrophilic and mixed primary cicatricial alopecias.

Primary cicatricial alopecias can be frustrating for both patients and physicians. Proper diagnosis guides more successful management of these challenging conditions. Part II will cover the remaining lymphocytic primary cicatricial alopecias, which include pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa, and keratosis follicularis spinulosa decalvans. It will also discuss the neutrophilic and mixed primary cicatricial alopecias, namely folliculitis decalvans, dissecting cellulitis, folliculitis keloidalis, folliculitis (acne) necrotica, and erosive pustular dermatosis.

Collagen cross-linking in recalcitrant corneal ulcers: A case series.

INTRODUCTION: Corneal ulcer is a leading cause of blindness worldwide. Many of these patients don't respond to conventional treatment with topical agents. Collagen cross-linking (CXL) has been suggested to avoid complications requiring emergency keratoplasty. SUBJECTS AND METHODS: Six eyes with presumed bacterial keratitis not responding to conventional treatment underwent CXL with ultraviolet A rays and transepithelial riboflavin. Patients with Descematocele and perforated ulcers were excluded. Preoperatively and postoperatively slit lamp examination of cornea and visual acuity recording was done. Postoperative outcome included subjective symptoms like relief in pain, photophobia, lacrimation and objective signs like improvement in epithelisation, corneal scarring with vascularisation. RESULTS: Four of the six eyes healed completely with scarring at 2 months follow-up. One of the patients developed Descematocele on 12 days which perforated later. Other patient developed Descematocele on 20 days post CXL. Of the subjective symptoms, pain and epiphora improved in all the patients except one. Photophobia improved only a week after CXL in four out of six patients. Epithelial defect completely healed over time in four out of six cases. All the cases who responded to treatment developed superficial and deep vascularisation of the cornea. Decrease in corneal edema and scarring was noted in four out of the six cases. CONCLUSION: The collagen cross-linking has a beneficial role as an adjuvant to medical therapy in recalcitrant bacterial keratitis. It helps in relief of pain and healing of ulcer. Larger randomized control trails with longer follow-up are required to come to a definite conclusion.

First report of keratitis in familial cold autoinflammatory syndrome.

OBJECTIVE: To report corneal manifestations of familial cold autoinflammatory syndrome (FCAS) for the first time. DESIGN: small case series PARTICIPANTS: Medical records of three members of a single family were reviewed after obtaining institutional review board (IRB) approval and informed consent. METHODS: All three members presented with a long history of maculopapular rash after cold exposure starting in childhood associated with nausea, low-grade fever, fatigue and arthralgia that lasted less than 24 hours. Their ocular manifestations consisted of ocular pain, photophobia and keratitis with subsequent stromal haziness. RESULTS: Patients underwent systemic therapy with canalinumab (Ilaris). They responded very well to repeated injections of Ilaris without side effects. CONCLUSIONS: FCAS causes lifelong debilitating effects that restrict patients' daily activities. Ilaris is an FDA-approved treatment for this condition and that typically results in dramatic improvement in clinical and laboratory measures of inflammation, and is well tolerated. Our report is the first small case series of FCAS with keratitis that responded to Ilaris beautifully.

Acute anterior uveitis following intravitreal injection of bevacizumab.

BACKGROUND AND OBJECTIVE: To report five cases of iritis after intravitreal injection of bevacizumab. PATIENTS AND METHODS: The clinical charts of patients who received intravitreal injections of bevacizumab or ranibizumab from January 2009 to September 2011 by one physician were retrospectively reviewed. RESULTS: A total of 1,097 injections of bevacizumab and 571 of ranibizumab were administered. Five patients developed acute anterior uveitis and presented with severe pain, photophobia, conjunctival injection, and anterior chamber reaction 2 to 24 hours after intravitreal injection of bevacizumab. All five patients were treated with topical corticosteroids with rapid resolution of the inflammation. CONCLUSION: Although uncommon, acute iritis is a complication of intravitreal injection of bevacizumab.

Topical bromfenac 0.09% vs. ketorolac 0.4% for the control of pain, photophobia, and discomfort following PRK.

PURPOSE: To compare the efficacy of two topical nonsteroidal anti-inflammatory drugs with regards to the control of pain, burning, photophobia, foreign body sensation, and epithelial healing rates in patients who underwent photorefractive keratectomy (PRK). METHODS: Two hundred twelve eyes were randomized to receive topical postoperative ketorolac 0.4% four times daily (Acular LS, Allergan) or bromfenac 0.09% twice daily (Xibrom, ISTA Pharmaceuticals) in an open label trial. Patients having both eyes treated received ketorolac in one eye and bromfenac in the other. The epithelium was removed using the 8.4-mm Amoils brush (Innovative Excimer Solutions), and various laser beam platforms were permitted for the surgery. Investigated drugs were applied after a bandage contact lens (Acuvue Oasys, Johnson & Johnson Vision Care) was fitted. All patients received postoperative cold saline (balanced saline solution [BSS]), prednisolone acetate 1.0% (Pred Forte, Allergan), gatifloxacin ophthalmic solution 0.3% (Zymar, Allergan), and in some cases, mitomycin C 0.02% (MMC). Patients recorded postoperative results for pain, photophobia, burning, and foreign-body sensation on a visual linear analog scale. During postoperative follow-up, the corneal epithelial defect was measured. RESULTS: Two hundred twelve eyes from 149 patients were enrolled in the study. Of these eyes, 105 received bromfenac and 107 received ketorolac. No significant differences were noted in postoperative pain, burning, foreign-body sensation, and photophobia between the two drug populations at any time during the study or overall. There were no drug-related adverse events or differences in epithelial healing rates for either drug. CONCLUSIONS: No significant differences were observed between the use of bromfenac (twice daily) and ketorolac (four times daily) with regard to postoperative PRK discomfort and safety when combined with postoperative measures such as cold BSS and a bandage contact lens.

Comparison of the analgesic efficacy and safety of nepafenac ophthalmic suspension compared with diclofenac ophthalmic solution for ocular pain and photophobia after excimer laser surgery: a phase II, randomized, double-masked trial.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of nepafenac ophthalmic suspension 0.03% and 0.1% for the treatment of postoperative pain and photophobia in patients undergoing excimer photoreactive keratectomy (PRK). METHODS: In this 7-day, randomized, double-masked, parallel-group trial at 2 sites, patients undergoing PRK surgery were randomly assigned to receive nepafenac ophthalmic suspension 0.03% or 0.1%, or diclofenac sodium ophthalmic solution 0.1%. Patients were treated on day 0 (surgery) and day 1 (the day after surgery). The dose regimen for all 3 treatments was the same. On day 0, patients received 2 drops in the operative eye -1 hour before surgery; 2 drops within 1 hour after surgery; 1 drop -4 hours after the first postoperative dose; and 1 drop -8 hours after the first postoperative dose. On day 1, patients instilled 1 drop of study drug QID. Thereafter, the study medication was discontinued. In the perioperative period, study personnel instilled the drops. The patients instilled the drops when they went home. Patients recorded pain and photophobia from day 0 through day 2, rating pain from 0 to 9 on a visual analog scale (0=none, 9=extreme) and photophobia from 0 to 3 on an ordinal, categoric scale (0=none, 3=severe). Patients were permitted to take acetaminophen 500 mg as needed for pain. They returned for postoperative follow-up visits on days 1, 3, and 7. Adverse events were documented when reported by the patients themselves, and when study personnel asked about specific events. RESULTS: Sixty patients (20 per group) were enrolled. On the day of surgery, there were no significant differences between groups, except at 3 hours after surgery, when the nepafenac 0.03% group had a significantly higher mean pain score than the nepafenac 0.1% group (4.0 vs 3.0; P<0.038). On day 2, the nepafenac 0.1% group had less pain at bedtime than the diclofenac group (mean score, 1.9 vs 3.1; P<0.024) and less photophobia in the morning (mean score, 1.2 vs 1.8; P<0.023). For the nepafenac 0.03% group, the mean pain and mean photophobia scores were 2.5 and 1.6, respectively. There were no significant differences between the 3 treatment groups in the proportion of patients who took acetaminophen for pain at any time point (P=NS). There was no statistically significant difference in corneal re-epithelialization rates among the 3 groups. Adverse events were infrequent, and no serious adverse events occurred. Two ocular adverse events related to therapy occurred: a corneal infiltrate in 1 patient in the nepafenac 0.03% group; and ocular discomfort in 1 patient in the nepafenac 0.1% group. Both patients continued the study. CONCLUSIONS: Both nepafenac 0.03% and 0.1% were effective for treatment of pain and photophobia in these patients undergoing PRK surgery. There was no difference in the proportion of patients who took rescue acetaminophen for pain. All treatments were well tolerated in these patients.

Successful use of topical cysteamine formulated from the oral preparation in a child with keratopathy secondary to cystinosis.

PURPOSE: To report the successful use of topical cysteamine formulated from the oral preparation in the treatment of severe photophobia from corneal crystal deposition in cystinosis. DESIGN: Interventional case report. METHODS: Retrospective chart review. RESULTS: An 8-year-old boy with nephropathic cystinosis was experiencing debilitating and worsening photophobia from corneal crystal deposition. Because no parenteral cysteamine was available nationally, the oral capsule was used to formulate an ophthalmic preparation for compassionate use. After 8 months of topical application, the patient has marked improvement of his corneal disease, both subjectively and objectively. CONCLUSIONS: In situations of need, there is a role for the formulation of ophthalmic cysteamine from its oral preparation.