Imtiaz A. Chaudhry

AMPHETAMINE BEHAVIORAL SENSITIZATION AND THE EXCITATORY AMINO ACIDS

The effects of 8 selective neuroeffector agonists and antagonists were measured in mice in order to identify specific functional changes associated with behavioral sensitization to amphetamine-induced stereotypy. The changes observed included a decreased convulsive threshold to N-methyl-DL-aspartic acid, an increased convulsive threshold to bicuculline, and an increased head-twitch response to 5-hydroxytryptophan. Of these effects, only the persistence of the two convulsive threshold changes correlated with the persistence of the behavioral sensitization. The induction of behavioral sensitization was blocked by haloperidol, dizocilpine or ketamine, but not affected by cyproheptadine or diazepam: therefore, the mechanism of the enhanced responsiveness involves not only a functional dopamine system, but also a functional N-methyl-D-aspartic acid component of the excitatory amino acid system. The block of behavioral sensitization also prevented the amphetamine-induced changes in the convulsive thresholds. Finally, neither ketamine nor dizocilpine affected the expression of the enhanced response in the behaviorally sensitized animals. The data indicate that the characteristics of amphetamine behavioral sensitization to stereotypy are similar to those of long-term potentiation.

Carotid cavernous fistula: Ophthalmological implications

Carotid cavernous fistula (CCF) is an abnormal communication between the cavernous sinus and the carotid arterial system. A CCF can be due to a direct connection between the cavernous segment of the internal carotid artery and the cavernous sinus, or a communication between the cavernous sinus, and one or more meningeal branches of the internal carotid artery, external carotid artery or both. These fistulas may be divided into spontaneous or traumatic in relation to cause and direct or dural in relation to angiographic findings. The dural fistulas usually have low rates of arterial blood flow and may be difficult to diagnose without angiography. Patients with CCF may initially present to an ophthalmologist with decreased vision, conjunctival chemosis, external ophthalmoplegia and proptosis. Patients with CCF may have predisposing causes, which need to be elicited. Radiological features may be helpful in confirming the diagnosis and determining possible intervention. Patients with any associated visual impairment or ocular conditions, such as glaucoma, need to be identified and treated. Based on patients signs and symptoms, timely intervention is mandatory to prevent morbidity or mortality. The conventional treatments include carotid ligation and embolization, with minimal significant morbidity or mortality. Ophthalmologist may be the first physician to encounter a patient with clinical manifestations of CCF, and this review article should help in understanding the clinical features of CCF, current diagnostic approach, usefulness of the available imaging modalities, possible modes of treatment and expected outcome.

Epidemiology of giant cell arteritis in an Arab population: a 22-year study

Objective: To study the epidemiology of biopsy-proven giant-cell arteritis (GCA) in an Arab population with clinical features suggestive of GCA. Methods: Clinical records of 102 patients who underwent temporal artery biopsy (TAB) at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia from January 1983 to December 2004 were reviewed. Results: Among the 56 men and 46 women who had TAB, 7 (6.8%) had biopsy-proven GCA. The mean (SD) age of the biopsy-positive group (71.7 (8.6) years) was higher than in the biopsy-negative group (65 (9.8) years; p = 0.005). None of the untreated patients with a negative TAB developed additional symptoms that are typical of GCA. Conclusion: The small absolute number of biopsy-proven cases of GCA implies a relatively low incidence of GCA in Arab population, confirming previous observations that GCA occurs primarily in the Caucasian population.

Bacteriology of chronic dacryocystitis in a tertiary eye care center.

Purpose: To determine the current bacteriology of adult chronic dacryocystitis in a tertiary eye care center and compare it with previously reported studies. Methods: Clinical and microbiological records of patients with diagnosis of chronic dacryocystitis between January 1999 and March 2002 were reviewed for age, sex, lacrimal sac side involved, and culture results. Patients younger than 16 years of age and patients who were receiving any systemic or topical antibiotics were excluded from the study. Results: One hundred eighty-eight adult patients with an average age of 50.5 years (range, 16 to 91 years), who had a diagnosis of chronic dacryocystitis, were identified. The study was predominated by female subjects (65.4%). Of the cultures from the nasolacrimal sac, 183 (97.3%) were positive for bacteria, with an average of 2.3 (1 to 6) microorganisms. More than 2 microorganisms were present in 66.1% of the cultures, whereas a single microorganism was recovered from 33.9% of the cultures. The majority of microorganisms in our study were Gram-positive bacteria, representing 53.7% of the overall microorganisms cultured with a predominance of Staphylococcus species. Gram-negative bacteria were recovered from 26.0% of the specimens with predominance of Haemophilus influenzae. Anaerobic microorganisms were present in 19.1% of the samples. The most frequently isolated anaerobic microorganisms were Propionibacterium acne and Peptostreptococcus species. Conclusions: Several bacterial species may be involved in the pathogenesis of chronic dacryocystitis in adults, and the majority of patients harbor multiple microorganisms in their nasolacrimal sacs. The high rate of microorganism-positive lacrimal sac cultures suggests that adult patients should be treated for their infection before any intraocular surgery because of the potential risk of infection.

Orbital pseudotumor: distinct diagnostic features and management.

Purpose: To provide an overview of the spectrum of diseases known as ‘idiopathic orbital inflammatory syndrome’ also known as orbital pseudotumor, with emphasis on specific diagnostic challenges in the evaluation and management of patients with this disorder. Methods: Review of the relevant literature and summarize recent findings regarding the epidemiology, diagnosis, pathophysiology and treatment of orbital pseudotumor. Results: Orbital pseudotumor is a benign intraorbital process confined to the orbit but extra orbital involvement can occur. It is among the 3rd most common orbital diseases along with thyroid orbitopathy and lymphoproliferative disorder and accounts for 5-10% of orbital processes. Clinically, orbital pseudotumor has been categorized as myositis, dacryoadenitis, anterior, apical and diffuse process. Patients may present with diplopia, conjunctival chemosis, proptosis or abnormal computed tomography scan (CT-scan) findings. Patients may also have associated optic neuropathy. Diagnosis is based on careful history, ultrasonography (U/S), CT-scan and magnetic resonance imaging (MRI) studies which may also provide prognostic information. Treatment consists of systemic corticosteroids in the form of oral or intravenous administration. Confirmation is made by orbital biopsy. In addition to radiation, cytotoxic agents, immunosuppressant, IV immunoglobulin, biological therapy, TNF-alpha inhibitor monoclonal antibody and Mycophenolate Moftil have been found to be useful in the management of refractory orbital pseudotumor. Conclusion: Understanding of the clinical features of patients with orbital pseudotumor, differentiating it from other orbital processes by use of imaging techniques and timely implementation of available treatment strategies may help prevent visual loss and associated morbidity from this condition.

L-carnitine protects human retinal pigment epithelial cells from oxidative damage.

Purpose: To determine the efficacy of L-carnitine (LC) against oxidative changes in human retinal pigment epithelium (RPE) cells. Methods: The RPE cells from human donor eyes were cultured in Hams F-10 medium. The effect of LC on H2O2-induced morphologic changes in the RPE cells was analyzed by light microscopy. Reduction in cell death after the impact of LC treatment on H2O2-treated cells was analyzed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. In addition, the effect of H2O2 on the activity of RPE-antioxidant enzymes, glutathione (GSH) and superoxide dismutase (SOD), and LC-induced protection was also determined. Results: LC protected the RPE cells by inhibiting the peroxide-induced cytopathic effect from 50% to 10%. Nuclear condensation observed in 40% of the H2O2-treated cells decreased to 20% after LC treatment. The MTT assays demonstrated that 100 μM oxidant caused appreciable cell death, which was reduced by LC treatment; however, 100% protection was not achieved. Significant peroxide-induced cell death was seen within 5 hr of H2O2 treatment, and a quantifiable reduction was observed after LC treatment for a similar time period. The change in the antioxidant potential of the RPE induced by oxidative stress was restored by LC treatment, as demonstrated by an increase in GSH and SOD activities. Conclusions: LC is capable of protecting the RPE cells from H2O2-induced oxidative damage, implying that micronutrients can have a positive effect and can play an important role in the treatment of oxidation-induced ocular disorders. Further studies are needed to understand the mechanism of LC-induced protection to the RPE cells.

Glaucoma and Globe Enlargement Associated with Neurofibromatosis Type 1

OBJECTIVE To describe the features of glaucoma and globe enlargement sometimes associated with neurofibromatosis type 1 (NF1). DESIGN Single institution, retrospective, and cross-sectional study. PARTICIPANTS Eighty medical records of patients treated at King Khaled Eye Specialist Hospital in Saudi Arabia with NF1 were reviewed, and 46 patients were examined. METHODS We reviewed the charts of patients with NF1 and examined available individuals, including gonioscopy, axial length, and ultrasound biomicroscopy in appropriate patients. MAIN OUTCOME MEASURES Presence and type of glaucoma, anterior chamber angle abnormalities, globe axial length, ultrasound biomicroscopy, and visual outcome. RESULTS Two patient groups were identified: Group 1 had 56 patients with orbito-facial NF1, and group 2 had 24 patients with NF1 but without orbito-facial involvement. Group 1 included 13 patients with glaucoma (23%), which occurred only ipsilateral to the orbito-facial involvement and generally presented before age 3 years. Glaucoma surgery was required in all of these patients, and visual prognosis was poor. In group 1, mean axial length on the side affected by NF1 was 29.8+/-4.1 mm in patients with glaucoma and 25.6+/-2.0 mm in patients without glaucoma. Patients with glaucoma (P<0.001) and without glaucoma (P<0.0001) in group 1 had significantly larger globes on the affected side. Group 2 patients had a mean axial length of 23.6+/-1.6 mm for both eyes without significant globe asymmetry. CONCLUSIONS In this Arab population, glaucoma associated with orbito-facial NF1 occurred less often than the 50% rate that is typically cited. Glaucoma presented early in life and only in patients with ipsilateral orbito-facial involvement. Glaucoma in this setting was always associated with globe enlargement. Glaucoma required surgery, and visual prognosis was poor because of glaucoma and concurrent pathology. Globe enlargement was most severe when associated with glaucoma but also present on the side with orbito-facial involvement in patients without glaucoma. The presence of neurofibroma may induce globe enlargement on the affected side in orbito-facial NF1. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Inpatient preseptal cellulitis: experience from a tertiary eye care centre

Objective: To describe causes of preseptal cellulitis (PSC) and outcome of treatment in patients admitted to a tertiary eye-care centre. Methods: A 15-year (January 1991 to December 2005) review of inpatients with clinical signs and symptoms or radiological evidence suggestive of PSC was conducted. Patients with infection anterior to the orbital septum which is characterised by acute onset of eyelid oedema, tenderness, erythema, warmth and chemosis were included in the study. Results: Among the 104 patients (male:female 64:40) fulfilling the diagnostic criteria for PSC, acute dacryocystitis (ADC) was the most common predisposing cause in 32.6% patients, followed by sinusitis/upper-respiratory infection (URI) in 28.8% and trauma/recent surgery in 27.8% patients. Fifty-per cent required surgical intervention including dacryocystorhinostomy/probing/stenting in 74% and abscess/chalazian drainage in 28.8%. In 38.5% of the patients who had surgical intervention, microbiological investigations were carried out, cultures were positive in 90%. Most common micro-organisms recovered included Staphylococcus and Streptococcus species followed by Haemophilus influenzae and Klebsiella pneumonia. Blood cultures were positive in two of the 34 patients in whom blood was drawn. Most patients responded to systemic antibiotics with resolution of PSC. Seven patients developed late complications which included subacute lid abscesses, eyelid necrosis and cicatricial ectropion. Conclusions: Sinusitis/URI, ADC and recent history of trauma/surgery were the most common cause of PSC in admitted patients. Although most patients responded to systemic antibiotics, surgical intervention was necessary in some patients to prevent associated complications.

Orbitofrontal cholesterol granuloma: Distinct diagnostic features and management

Purpose To describe the distinct clinical, radiologic, and histopathologic findings of orbitofrontal cholesterol granuloma and treatment approaches. We also present 2 atypical cases of cholesterol granuloma, one of which we believe represents the smallest and one of which the most extensive lesion among the previously reported cases in the literature. Methods The records of 8 patients with orbital cholesterol granuloma were reviewed retrospectively. Results Mean age at presentation was 45 years. Six of 8 patients were male. The most common symptom at presentation was proptosis (50%). Computerized tomography of orbits showed a lytic lesion in the superolateral bony orbit with an extraconal soft tissue mass in 2 patients and a cystic lesion eroding the superolateral orbital roof in 4 patients. One patient had a small lytic lesion in the frontal bone without associated soft tissue mass and one patient had a very large destructive mass with extensive intracranial and orbital extension. Magnetic resonance imaging was obtained in 2 patients and showed a non–contrast-enhancing lesion with high signal intensity on both T1- and T2-weighted images. Seven patients were treated by aspiration of the contents and curettage of the lining by an extraperiosteal approach through a subbrow incision. One patient who was clinically thought to have a frontal mucocele was treated by frontal sinus exploration, removal of the lesion, and obliteration of the sinus. Two of 7 patients required lateral orbitotomy for better exposure of the tumor. Only one patient had recurrent symptoms and required a second surgery. Conclusions Orbitofrontal cholesterol granulomas have typical clinical and radiologic features. Surgical excision has a high success rate with a low incidence of recurrence.

Congenital Ectropion Uvea and Mechanisms of Glaucoma in Neurofibromatosis Type 1:: New Insights

OBJECTIVE To describe the clinicopathologic features of congenital ectropion uvea associated with glaucoma in neurofibromatosis-1 (NF-1). DESIGN Retrospective case series. PARTICIPANTS AND CONTROLS Five cases of NF-1 associated with glaucoma, from which enucleated eyes were available, and 2 eye bank eyes used as controls. METHODS The clinical features and courses of these patients were reviewed. Formalin-fixed, paraffin-embedded eyes were examined by light and electron microscopy. Immunohistochemistry using antineurofibromin, anti-glial fibrillary acidic protein, and antivimentin was performed in 3 patients. Gene expression of the mitogen-activated protein kinase (MAPK) signaling pathway was examined in corneal endothelial cells in 1 patient. MAIN OUTCOME MEASURES Cause of glaucoma in patients with ectropion uvea and NF-1. RESULTS The age of patients at the time of glaucoma diagnosis ranged from birth to 13 years. Four of the 5 patients had megalocornea and buphthalmos at presentation. Ectropion uvea was noted clinically in 2 patients, but was demonstrated histopathologically in all 5 patients. On histopathologic examination, all patients had varying degrees of angle closure secondary to endothelialization of the anterior chamber angle. Uveal neurofibromas were noted in all patients; anteriorly displaced ciliary processes were noted in 4 of 5 patients who demonstrated ciliary body involvement with neurofibromas. Absence of Schlemms canal was observed. The endothelial cells lining the closed angle demonstrated positive stain results with the vimentin antibody. Positive antineurofibromin immunolabeling was detected in normal control corneal endothelium, but was absent in corneal endothelium in patients with endothelialization of the angle. Upregulation of genes from the MAPK signaling pathway was demonstrated in the corneal endothelial cells isolated from the NF-1 eyes. CONCLUSIONS Ectropion uvea in NF-1 glaucoma is secondary to endothelialization of the anterior chamber angle and is associated commonly with severe pediatric glaucoma in NF-1 patients. The endothelial cell proliferation may be related to overexpression of the Ras (Rat sarcoma)-MAPK genes in these eyes.