Alireza Dehghani

Differentiation of Human Embryonic Stem Cell–Derived Retinal Progenitors into Retinal Cells by Sonic Hedgehog and/or Retinal Pigmented Epithelium and Transplantation into the Subretinal Space of Sodium Iodate–Injected Rabbits

Transplantation of retinal cells has recently provided a promising therapeutic approach for retinal degeneration. Here, we differentiated initially retinal progenitors (RPs) from adherent feeder-free human embryonic stem cells (hESCs) with the use of defined media supplemented with a specific combination of growth factors. The differentiated RPs highly (>80%) expressed related molecular features that included Six3 at an early stage in addition to Crx, Rx, Pax6, Otx2, and Chx10 at later stage. Next, we examined the induction of photoreceptors by Shh and/or the coculture of rabbit retinal pigmented epithelium with hESCs-derived RPs. The differentiation of retinal cells was demonstrated by protein and gene expression in all groups. However, S-Opsin, a cone photoreceptor marker, had higher expression in the presence of Shh, whereas expressions of Gli and Hes1 decreased in the same group. Finally, hESC-derived RPs were treated with Shh transplanted into the subretinal space of sodium iodate-injected albino-type adult rabbits and analyzed 4 weeks later. Transplanted retinal cells survived, migrated into retinal layers, and restored a small but significant B-wave. The grafted cells expressed photoreceptor markers, S-Opsin and Rhodopsin. Our results indicate that putative hESC-derived retinal cells express related genes and proteins. Further, our results show that retinal-like cells can be useful replacements for photoreceptors in retinal diseases.

Extraction of retinal blood vessels by curvelet transform

This paper presents an efficient method for automatic extraction of blood vessels in retinal images to improve the detection of low contrast and narrow vessels. The proposed algorithm is composed of four steps: curvelet-based contrast enhancement, match filtering, curvelet-based edge extraction, and length filtering. In this base, after reconstruction of enhanced image from the modified curvelet coefficients, match filtering is used to intensify the blood vessels. Then we employ curvelet transform to segment vessels from its background and finally the length filtering is used to remove the misclassified pixels. The performance of algorithm is evaluated on DRIVE [1] databases and compared with those obtained from a hand-labeled ground truth. Since the curvelet transform is well-suited to handle curve discontinuities, we achieve an area under ROC curve of 0.9631 that demonstrates improved performance of proposed algorithm compared with known techniques.

A new curvelet transform based method for extraction of red lesions in digital color retinal images

Red lesions in the form of Microaneurysms (MAs) and Hemorrhages (HMs) are among the first explicit signs of diabetic retinopathy (DR). Hence robust detection of these lesions is an important diagnostic task in computer assistance systems. In this paper we present a new curvelet based algorithm to separate these red lesions from the rest of the color retinal image. In order to prevent fovea to be considered as red lesion, we introduce a new illumination equalization algorithm and apply that to green plane of retinal image. In the next stage, we apply digital curvelet transform (DCUT) to produced enhanced image and modify curvelet coefficients in order to lead red objects to zero. Then we separate these lesions as candidate region by applying an appropriate threshold. Finally, the total structure of blood vessel is extracted employing a curvelet-based technique and the false positives (FPs) are eliminated by subtracting the vessel structure from the candidate images. Experiments on 89 retinal images of diabetic patients indicate that we are able to achieve 94% sensitivity and 87% specificity in detection of red lesion.

Orbital Doppler Evaluation of Blood Flow Velocities in Optic Neuritis

Purpose To evaluate orbital blood flow velocities and optic nerve diameter with Doppler and gray-scale sonography in patients with acute unilateral optic neuritis (ON). Methods Orbital Doppler and gray-scale sonography was performed in 46 eyes of 23 patients aged 19- to 47-years with acute unilateral ON. ON was diagnosed by an ophthalmologist on the basis of clinical presentation, presence of decreased visual acuity and assessment of visual evoked potentials. The peak systolic velocity (PSV) and end-diastolic velocity (EDV), as well as the resistance index (RI) and pulsatile index (PI) of the ophthalmic artery (OA), central retinal artery (CRA), posterior ciliary arteries (PCAs) and optic nerve diameter were measured in both eyes. We compared results from affected and unaffected eyes using the paired t-test. The area under the receiver operating characteristic (ROC) curves was used to assess the diagnosis of ON based on measured blood flow parameters of the OA, CRA and PCAs and optic nerve diameter. Results The mean (standard deviation) optic nerve diameter in eyes with ON was 4.1 (0.8) mm, which was significantly larger than the 3.0 (0.4) mm diameter measured in unaffected control eyes (p < 0.001). There were no differences in average PSV, EDV, RI, or PI of the OA and CRA between affected and unaffected eyes (p > 0.05). The mean RI in the PCAs was slightly lower in the eyes with ON than in the contralateral eyes (0.60 vs. 0.64, p < 0.05). The area under the ROC curves indicated that optic nerve diameter was the best parameter for the diagnosis of ON. Conclusions Optic nerve diameter was related to ON, but orbital blood flow parameters were not.

Bilateral Angle-Closure Glaucoma in a Young Female Receiving Cabergoline: A Case Report

Purpose: To report a case of bilateral acute angle-closure glaucoma after oral administration of cabergoline for the treatment of galactorrhea. Methods: A diagnosis of secondary drug-induced angle-closure glaucoma was made in a patient with elevated intraocular pressure (IOP) and myopic refractive shift, which was confirmed by ultrasound biomicroscopy (UBM) of the ciliary body and anterior segment, sonography, and optical coherence tomography. The treatment included the discontinuation of the culprit drug and the administration of topical anti-glaucoma drops. The treatment course was followed with serial measurements of the IOP and refraction, and with performing UBM. Results: Five hours after he received a single 0.5-mg oral cabergoline tablet, the patient suffered from acute secondary angle-closure glaucoma and myopic refractive error. UBM demonstrated both effusion of the ciliary body and an anterior rotation of the iris-ciliary body. IOP was reduced 8 h after cessation of the causative agent and administration of anti-glaucoma drops. Refractive errors returned to normal levels after 8 days. Conclusion: Secondary acute angle-closure glaucoma has been reported to occur after the administration of some drugs. In this report, an attempt has been made to describe this adverse reaction after oral cabergoline intake.

Massive bilateral choroidal detachment induced by administration of topiramate.

Topiramate is a sulfa-derivative antiepileptic drug which is also used for other indications such as essential tremor. A 79-year-old male was admitted to our center due to acute bilateral painless decline of vision. One month before admission, he had experienced essential tremor and treatment with topiramate 50 mg/day and propranolol 40 mg/day. Best-corrected visual acuity was 20/800 OD and 20/600 OS. Both eyes had normal anterior chamber depths and irides. Intraocular pressure was 10 mm Hg in the right eye and 11 mm Hg in the left eye. Retinal examination showed notable choroidal detachments in all quadrants of the periphery, which were confirmed by ultrasonography. Refraction showed no myopic shift. The administration of topiramate was discontinued as a potential causative agent for this condition. During follow-up, choroidal detachment and visual acuity gradually resolved. In this study, we described the first case of isolated massive choroidal detachment induced by topiramate.

Myasthenia Gravis during the Course of Neuromyelitis Optica

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system that has been thought to be a severe subtype of multiple sclerosis for a long time. The discovery of aquaporin-4 (AQP4) antibody as a highly specific marker responsible for the pathogenesis of NMO, not only has made a revolutionary pace in establishing a serologic distinction between the two diseases, but it has also classified NMO as an antibody-mediated disorder. Similarly, myasthenia gravis (MG) is a well-known antibody-mediated disorder. In this report, we describe the case of a middle-aged female patient who experienced definite MG with an unclear clinical picture of chronic demyelinating disease that initially reflected the diagnosis of MS, but further imaging and paraclinical workup (e.g. positive AQP4 antibody test) revealed NMO. The coexistence of NMO and MG is previously described. However, this is the first case with NMO symptoms preceding the onset of MG. Of note, the development of MG occurred after a 2-year period of interferon β-1b (IFN β-1b) administration. This calls the question to mind of whether in our case MG is induced by the administration of interferon, instead of an original pathogenic link between MG and NMO. In other words, immunomodulatory treatments can slip the immunity towards T-helper II predominant pathways that can trigger MG. However, if we assume that such an explanation (i.e. increased susceptibility to autoantibody-mediated disorders) is true, our case can be considered the first case of NMO who developed MG following IFN β-1b treatment.

Orbital Doppler evaluation of blood flow velocities in patients with diabetic retinopathy.

BACKGROUND There have been conflicting results in relation to impaired ocular hemodynamics in the orbital vessels of patients with diabetic retinopathy (DR). Clarification of the early signs of retinopathy in diabetic patients is urgently needed. AIMS We aimed to evaluate orbital blood flow velocities using Doppler and gray-scale sonography in patients with DR, and to compare the results with those of their non-diabetic and diabetic peers without retinopathy. METHODS Orbital Doppler and gray-scale sonography were performed in 123 patients aged 29-77 who had been divided into 3 groups: non-diabetic controls (n = 25), diabetes and impaired glucose tolerance with minimal clinical retinopathy (n = 74), and diabetes with untreated non-proliferative retinopathy (n = 24). Retinopathy was diagnosed by an ophthalmologist on the basis of fundoscopic examination. The peak systolic (PSV) and end-diastolic (EDV) blood flow velocities, and the resistivity and pulsatile indices, of the ophthalmic artery, central retinal artery, posterior ciliary artery, and central retinal vein were measured. RESULTS Compared with healthy controls, the age-adjusted resistivity and pulsatile indices of the ophthalmic artery were significantly higher in patients with DR (p < 0.05). PSV and EDV of the posterior ciliary arteries were significantly lower in diabetic patients with DR. After further adjustment for age, gender, HbA1c, fasting plasma glucose, blood pressure, BMI, cholesterol, HDL, LDL, and triglycerides, only the resistivity index of the ophthalmic artery and the central retinal vein remained significantly higher in patients with DR compared with healthy controls (p < 0.005 after Bonferroni adjustment). CONCLUSIONS Resistivity index alteration of the ophthalmic artery and central retinal vein may be prevalent among patients with early changes in DR.

Endogenous Klebsiella endophthalmitis associated with liver abscess: first case report from iran.

Purpose: To report the first case of endogenous Klebsiella endophthalmitis associated with liver abscess in Iran. Case Report: A 79-year-old man was referred to our hospital due to severe pain and visual loss in the left eye. On physical examination, conjunctival hyperemia, corneal edema, hypopyon and severe vitreous cellular reaction were identified in the left eye; however, yellowish conjunctival discoloration was more apparent in the right eye. Abdominal CT scan showed a right liver lobe abscess that was confirmed by sonographically guided percutaneous liver mass biopsy. Blood, vitreous and liver mass aspirate cultures revealed Klebsiella pneumoniae growth. The patient was thus diagnosed with endogenous Klebsiella endophthalmitis secondary to bacteremia associated with liver abscess. Conclusion: This report suggests that, rather than being confined to Taiwan, endogenous endophthalmitis secondary to a liver abscess due to K. pneumoniae may be a global problem. Therefore, physicians should be aware of the possibility of endophthalmitis whenever a patient with K. pneumoniae liver abscess complains of ocular symptoms.

Ultrasonography in distinguishing optic neuritis from nonarteritic anterior ischemic optic neuropathy.

Background and Objectives: Optic neuritis (ON) and nonarteritic anterior ischemic optic neuropathy (NAION) have some overlapping clinical profiles. We evaluated the usefulness of B-scan ultrasonography in distinguishing ON from NAION by measuring diameter of the optic nerve. Materials and Methods: Consecutive patients with an acute noncompressive unilateral optic neuropathy with relative afferent pupillary defect and onset of visual loss during the last 2 weeks were included. Diagnosis of ON was based on age ≤ 35 years, orbital pain associated with eye movement, and no disk edema, and diagnosis of NAION was based on age ≥ 60 years, no orbital pain associated with eye movement, and presence of disk edema. Age- and gender-matched subjects without ocular disease were selected for comparison. The diameter of the optic nerve was measured by a single radiologist with B-scan ultrasonography. Results: In ON patients, the mean diameter of the affected nerve was significantly larger than that of the unaffected nerve and also larger than that of the right nerve of young controls; P < 0.05. In NAION patients, however, there was no significant difference between the mean diameter of the affected nerve and of the unaffected nerve or the right nerve of elderly controls; P > 0.05. Also, the diameter of the affected nerve was significantly larger in ON than in AION patients; P < 0.05. Conclusion: B-scan ultrasonography is helpful in the early stages of optic neuropathy to distinguish ON from NAION in those cases for which the diagnosis is still uncertain after clinical evaluation.