Did Edgar Degas have Stargardt disease?

Renowned French painter Edgar Degas suffered of progressive light sensitivity and blurred central vision in both eyes, which affected his life and art in many ways. A first cousin from his mother's side, Estelle Musson of New Orleans also lost vision in a similar fashion at a comparable age. We postulated that Edgar and Estelle shared the same retinal pathology that possibly developed in a hereditary fashion, and we were interested whether any of their living family descendants might carry ABCA4 mutations to test the possibility that Edgar Degas may have had Stargardt disease.Edgar was never married and had no children, but Estelle had five children, four of whom from her marriage to Edgar's younger brother, and there are several descendants still living in New Orleans area. Genetic testing on five of Estelle's great grandchildren (Edgar's great grandnieces) were performed searching for ABCA4 mutations.We could not document any disease-causing variations in the ABCA4 gene in any of the descendants and therefore concluded that Edgar Degas most likely did not have Stargardt disease. Estelle and Edgar may have shared a different hereditary disease or have had two different retinal dystrophies or had another eye disease, including the unlikely possibility of inflammatory disease.

A prospective comparison of fine-needle aspiration cytopathology and histopathology in the diagnosis of orbital mass lesions.

AIM: To assess the diagnostic value of the orbital fine needle aspiration biopsy (FNAB) with an in vitro technique, eliminating the sampling error. DESIGN: Prospective, non-randomised, interventional case series. METHODS: Sixty-eight patients were studied prospectively in institutional clinical practices. Immediately after excision of orbital mass lesions, the removed tissue was stabilised under the hand of the surgeon and biopsied with a 23- or 25-gauge needle. The samples were processed for cytopathological examination with Cytospin. The excised specimens were then submitted for routine histological examination. The cytopathological diagnoses were compared with the final histopathological diagnoses. RESULTS: Six out of 68 lesions were excluded and the remaining 62 cases were divided into four groups as primary malignant, primary benign, secondary malignant and inflammatory lesions, based on histopathological diagnoses. In 43 cases the cytopathological and histopathological diagnoses were the same, with a concordance rate of 69%. Among the malignant tumours, the cytopathological diagnoses correlated with the histopathological diagnoses in 14/14 and 17/27 cases of metastatic/secondary and primary orbital malignancies, respectively. Of 11 primary benign tumours, two cytopathological diagnoses correlated with histopathology. In inflammatory lesions, the cytopathological diagnoses were matched with the histopathological diagnoses in 10/10 biopsies. CONCLUSION: Even when the sampling error is eliminated with an "in vitro FNAB" technique, the concordance rates between histopathological and cytopathological diagnoses varied considerably among different types of orbital mass lesions. FNAB diagnoses were most reliable in metastatic and secondary malignancies and inflammatory lesions, and least reliable in benign orbital neoplasms and cysts.

Computer-assisted image-guided orbit surgery.

PURPOSE: Modern stereotaxy utilizes preoperative computed tomography (CT) and magnetic resonance imaging (MRI) to provide accurate localization information which can be very helpful in orbital surgery. The purpose of this report is to evaluate the usefulness of stereotactic surgery and application of this procedure in the orbit. METHODS: Interventional case series of three patients with orbital tumors. All patients had tumor resection with the utilization of two frameless stereotactic systems: Cygnus and Stealth Station. RESULTS: The applications of image-guided stereotactic surgery proved to be beneficial in three extensive orbital tumors, including optic nerve glioma, recurrent pleomorphic adenoma of lacrimal gland, and secondary orbital meningioma. CONCLUSIONS: The interactive nature of image guidance can be useful in orbital surgery to orient the surgeon to the exact location within the surgical field and to determine the tumor margins.

Altered fine structures of corneal and skeletal keratan sulfate and chondroitin/dermatan sulfate in macular corneal dystrophy.

The content and fine structure of keratan and chondroitin/dermatan sulfate in normal human corneas and corneas affected by macular corneal dystrophies (MCD) types I and II were examined by fluorophore-assisted carbohydrate electrophoresis. Normal tissues (n = 11) contained 15 microg of keratan sulfate and 8 microg of chondroitin/dermatan sulfate per mg dry weight. Keratan sulfates consisted of approximately 4% unsulfated, 42% monosulfated, and 54% disulfated disaccharides with number of average chain lengths of approximately 14 disaccharides. Chondroitin/dermatan sulfates were significantly longer, approximately 40 disaccharides per chain, and consisted of approximately 64% unsulfated, 28% 4-sulfated, and 8% 6-sulfated disaccharides. The fine structural parameters were altered in all diseased tissues. Keratan sulfate chain size was reduced to 3-4 disaccharides; chain sulfation was absent in MCD type I corneas and cartilages, and sulfation of both GlcNAc and Gal was significantly reduced in MCD type II. Chondroitin/dermatan sulfate chain sizes were also decreased in all diseased corneas to approximately 15 disaccharides, and the contents of 4- and 6-sulfated disaccharides were proportionally increased. Tissue concentrations (nanomole of chains per mg dry weight) of all glycosaminoglycan types were affected in the disease types. Keratan sulfate chain concentrations were reduced by approximately 24 and approximately 75% in type I corneas and cartilages, respectively, and by approximately 50% in type II corneas. Conversely, chondroitin/dermatan sulfate chain concentrations were increased by 60-70% in types I and II corneas. Such changes imply a modified tissue content of individual proteoglycans and/or an altered efficiency of chain substitution on the core proteins. Together with the finding that hyaluronan, not normally present in healthy adult corneas, was also detected in both disease subtypes, the data support the conclusion that a wide range of keratocyte-specific proteoglycan and glycosaminoglycan remodeling processes are activated during degeneration of the stromal matrix in the macular corneal dystrophies.

Sclerokeratitis: an unusual presentation of squamous cell carcinoma of the conjunctiva.

OBJECTIVE: To describe three cases of squamous cell carcinoma of the conjunctiva presenting with corneal and scleral inflammation, thinning, and perforation without any tumor formation. DESIGN: Three case reports. PARTICIPANTS: Three male subjects aged 76, 66, and 61 years. INTERVENTION: The subjects had symptoms of external ocular inflammation with focal corneal or scleral thinning and inflammation, as well as interstitial keratitis in two cases. Initial diagnosis of sclerokeratitis with limbal thinning was made in all three in addition to a pterygium in case 2. MAIN OUTCOME MEASURES: Diagnosis of the carcinoma was delayed for 2 to 24 months in two cases, whereas case 2 was diagnosed on excision of a pterygium from the involved area. RESULTS: All subjects developed intraocular extension after further scleral thinning and perforation without tumefaction. CONCLUSIONS: Squamous cell carcinoma of the conjunctiva may be seen without a distinct mass and can masquerade as sclerokeratitis, scleromalacia, or interstitial keratitis. It seems that diffuse growth with inflammation leads to thinning, necrosis, and perforation of the ocular wall with resultant intraocular spread. Squamous cell carcinoma should be considered in the differential diagnosis of corneal and scleral thinning, perforation, and inflammation of unknown cause, especially in the older male subject.

Relation between p53 overexpression and clinical behavior of ocular/orbital invasion of conjunctival squamous cell carcinoma.

PURPOSE: To investigate the p53 gene as a prognostic indicator in conjunctival squamous cell carcinoma. METHODS: Medical records were reviewed and histopathology slides were examined to verify the diagnosis and grade of tumor differentiation in a retrospective case series of 12 patients with "invasive" and 11 patients with "noninvasive" conjunctival squamous cell carcinoma. The p53 antigen was detected using the streptavidin biotin-alkaline phosphatase immunostaining method. Statistical analysis was performed using the Fisher exact test. RESULTS: p53 overexpression was present in 14 cases (approximately 60%). Eight and 6 of 14 p53-positive tumors were invasive and noninvasive, respectively. All patients with recurrence (two), recurrence and metastasis (two), metastasis (three), and death with tumor dissemination (three) had p53 overexpression. Of all adverse outcomes, only two cases with recurrence were p53 negative: no metastasis or death with dissemination was seen in p53-negative tumor cases. CONCLUSIONS: There was no statistical relationship between p53 overexpression and age, sex, location, invasiveness, or histopathologic differentiation of the tumor; however, a significant association existed between p53 positivity and adverse clinical behavior (p = 0.014).

The relationship between human papillomavirus and p53 gene in conjunctival squamous cell carcinoma.

PURPOSE: The p53 tumor-suppressor gene has been documented to exist in mutated forms in many types of squamous cell carcinoma in the body. Also in conjunctival squamous cell carcinoma, human papillomavirus (HPV) is accepted as an oncogenic factor. The objective of our study was to establish a correlation between p53 overexpression and the presence of HPV infection within tumor tissues from patients with conjunctival squamous cell carcinoma. METHODS: Tissue sections obtained from paraffin-embedded conjunctival squamous cell carcinoma specimens from 23 patients were examined with light microscopy, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: Seventy-eight percent of tumors were positive for p53, whereas 22% were positive for HPV. The proportion of patients positive for both p53 and HPV was 17%, whereas another 17% of the patients were negative for both p53 and HPV. Therefore no significant disproportion was found in the distribution of patients' HPV status and p53 status (p = 1.00). No significant correlation or linear association was found between the HPV status and p53 status (r = 0.022; p = 0.920). CONCLUSION: We could not show any statistical association between abnormal p53 gene-product expression by immunohistochemistry in conjunctival squamous cell carcinomas and HPV infection by PCR detection techniques.

Nasolacrimal tuberculosis in a patient with conjunctivodacryocystorhinostomy.

PURPOSE: To present an unusual case of nasolacrimal tuberculosis that was diagnosed with polymerase chain reaction (PCR) and to discuss the role of PCR as a diagnostic aid. METHODS: Case presentation with diagnostic modalities including PCR, cytopathologic, and histopathologic examinations with special stains. RESULTS: A 40-year-old woman with bilateral lacrimal drainage system obstruction underwent a right dacryocystorhinostomy with stents and left conjunctivodacryocystorhinostomy with Jones bypass tube. Although the findings of direct and endoscopic examinations of the nasal cavity were within normal limits, the tissue removed during surgery from the middle turbinate revealed caseating granulomatous lesions on histopathologic examination. Acid-fast organisms were demonstrated in postoperative nasal washings, and Mycobacterium tuberculosis infection was confirmed with PCR. CONCLUSION: Primary tuberculosis of the nasolacrimal mucosa is rare, and its occurrence without any symptoms, as in this patient, is even less frequent. The most interesting aspect of this case was the identification of the M. tuberculosis DNA in the mucosa of anterior turbinate and fibrous tissue within the previous surgical site. Histopathologically, the presence of caseating granulomas was seen only in the nasal mucosa, indicating that PCR may be of use in identifying the causative organism even in the absence of typical histopathologic features.

Penetrating orbital injury with organic foreign bodies.

OBJECTIVE: The authors reviewed the clinical features, diagnostic workup, and management of patients of penetrating orbital injuries with retained organic foreign bodies. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Nineteen patients (15 males, 4 females) with penetrating orbital injuries due to organic foreign bodies. RESULTS: The series included 15 (78.9%) males and 4 (21.1%) females who ranged in age from 6 months to 40 years (mean = 14.6 years); 12 (63.2%) patients were younger than 12 years of age. Twelve (63.2%) right and 7 (36.8%) left orbits were involved. Time between injury and presentation varied from a few hours to 9 months. Most common injury site was the superior orbit in 11 (57.9%) patients leading to abnormal extraocular motility (84.2%), proptosis (68.4%), and upper lid ptosis (47.4%). Associated pathologies also included acute cellulitis in 11, orbitocutaneous fistula in 5, and osteomyelitis in 2 patients. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) identified the foreign bodies in 42% and 57% of the patients, respectively. CONCLUSION: Preoperative identification of the foreign material in the orbit was found to be very helpful for patient management but was only possible in approximately 50% of our cases with the use of CT and MRI. The vision in our patients usually improved shortly after treatment; the long-term complications more often included extraocular muscle and eyelid motility problems and periorbital scarring.

Pharmacokinetics of azithromycinin rabbit lacrimal glands and conjunctiv a.

PURPOSE AND BACKGROUND: To measure azithromycin levels in rabbit lacrimal and Harder glands, conjunctiva and plasma after a single oral dose of 20 mg/kg. Drug levels in lacrimal gland tissue are significant in trachoma because the gland may be involved in the disease process and it is the source of tears by which the drug is carried to the external eye. METHODS: Lacrimal and Harder glands, conjunctiva and plasma were collected from New Zealand white female rabbits at 24, 48, 72, 96 and 144 h following a single oral dose of azithromycin (20 mg/kg). Azithromycin levels in tissue and plasma were measured using high-performance liquid chromatography (HPLC) electrochemical detection. RESULTS: Azithromycin levels peaked within the first 24 h in all tissues and plasma assayed. The highest concentration was in the lacrimal gland (6.2 microg/g, SD +/- 0.8), followed by Harder gland (4.4 microg/g, SD +/- 0.8), conjunctiva (0. 9 microg/g, SD +/- 0.5) and plasma (0.06 microg/g, SD +/- 0.03). These concentrations reached their lowest measured levels at 120 and 144 h. CONCLUSION: Azithromycin levels measured throughout the 144 h after dosing were consistently above the minimum inhibitory range (MIC) for Chlamydia trachomatis (0.03-0.25 microg/ml) in the lacrimal glands, while the conjunctiva maintained a concentration above the MIC for 96 h and stayed within MIC levels for 144 h.

Simultaneous high-performance liquid chromatography analysis of azithromycin and two of its metabolites in human tears and plasma.

This article describes a high-performance liquid chromatographic (HPLC) method for the measurement of azithromycin (AZI) and two of its metabolites, 9a-N-desmethylazithromycin (ADES) and N-desmethylazithromycin (NDES), in human tears and plasma. The drug, metabolites, and internal standard (n-propylazithromycin [IS]) were detected electrochemically after injection of the extracted sample into the HPLC system. The peak height ratio (AZI, ADES, or NDES to IS) varied linearly, with concentrations in the ranges of 0.1 mg/L to 2.0 mg/L (tears) and 0.01 mg/L to 2.0 mg/L (plasma) of AZI, ADES, and NDES; the correlation coefficient (r) was more than 0.994 mg/L for all of the compounds (n=6). The analysis of tear samples collected at different intervals within 12 hours to 144 hours after a dose of 20 mg/kg of AZI from a trachoma patient yielded concentrations ranging from 1.52 mg/L to 0.34 mg/L for AZI, 0.79 mg/L to 0.27 mg/L for ADES, and 1.99 mg/L to less than 0.20 mg/L for NDES. The concentration of AZI in plasma ranged from 0.15 mg/L to 0.01 mg/L, whereas ADES and NDES were undetectable.

Clinical and morphological features of Waardenburg syndrome type II.

Evaluation of 4-month-old girl who presented with congenital cataracts revealed heterochromia iridis, fundus hypopigmentation, residual white forelock and sensory neural hearing loss--findings consistent with Waardenburg syndrome type II. Bilateral peripheral iridectomies performed at lensectomy provided tissue for evaluation. Light microscopy revealed fewer melanocytes in the blue iris than in the brown. Electron microscopic examination showed a significant (p = 0.0001) reduction in melanosome size in the blue iris, and the nerve endings contained fewer vesicles. A defect in neural crest cell migration and melanin synthesis may be responsible for the heterochromia iridis seen in Waardenburg syndrome type II.

Retinoblastoma associated orbital cellulitis.

AIM: Preseptal and orbital cellulitis are rare presenting features of intraocular retinoblastoma. The objectives of this study were to determine the frequency of retinoblastoma associated cellulitis, as well as to review its clinical and histopathological features. METHODS: The medical records of 292 retinoblastoma patients in the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia were reviewed. Those indicating a history of, or presenting with, cellulitis were retrieved and their clinical, radiological, and histopathological variables were assessed. Patients with definite extraocular tumour extension on clinical or radiological examination were excluded. RESULTS: 14 patients were found to have retinoblastoma associated cellulitis (4.8%); nine had bilateral and five had unilateral retinoblastoma. Conjunctival and blood cultures were performed in 10 cases and were negative. 10 children were treated with intravenous steroids, often in conjunction with antibiotics, resulting in a prompt decrease in inflammation. Three other children were treated with antibiotics alone and one received no treatment. Computed tomographic scanning depicted large intraocular tumours occupying between 80% and 100% of the globe in each case. In eight patients, periocular inflammation was radiologically interpreted as possible extraocular extension. In one patient serial computed tomographic scanning showed a reduction in intraocular calcification over time which occurred in the presence of cellulitis, 12 patients underwent enucleation and histopathological examination revealed large necrotic, poorly differentiated tumours associated with uveal involvement and early optic nerve invasion. Focal perilimbal destruction was seen in one patient, and in another peripapillary extrascleral extension was present. 12 patients are alive with a mean follow up of 56.4 months. CONCLUSIONS: Radiological evaluation of scleral integrity may be hindered by periocular inflammatory changes. The orbital cellulitis correlated well with the presence of advanced intraocular retinoblastoma with massive necrosis and anterior chamber involvement. In the majority of patients, cellulitis was not indicative of an extension of retinoblastoma into the orbit. Intravenous steroid treatment reduced orbital inflammation, facilitating examination and subsequent enucleation.

Detection of optic nerve involvement in retinoblastoma with enhanced computed tomography.

PURPOSE: The study was designed to evaluate the value of enhanced computed tomography (CT) as a non-invasive test in the detection of optic nerve invasion in retinoblastoma. METHODS: Nineteen eyes in 17 consecutive retinoblastoma patients underwent CT studies performed with high spatial resolution (512 x 512) and 1.5 mm sections, both with enhancement and without enhancement. If the central retinal vessels (CRV) were subjectively visualised with intravenous enhancement, the optic nerve was considered to be free of retinoblastoma. Nineteen enucleated globes were processed for histopathology, and the optic disc and nerve examined with light microscopy for the presence or absence of tumour and the level of involvement. RESULTS: The correlation between the visualisation of CRV and the presence or absence of optic nerve involvement histopathologically was found to be highly significant (p = 0.0006, Fisher exact test). CONCLUSION: In high spatial resolution CT with enhancement and 1.5 mm or thinner sections, non-visualisation of the CRV appears to be a reliable indicator of optic nerve invasion with retinoblastoma.

Porous polyethylene orbital implant in patients with retinoblastoma.

OBJECTIVE: The purpose of the study was to assess integration of porous polyethylene allografts in 37 anophthalmic sockets of retinoblastoma enucleations. DESIGN: A clinical review. PARTICIPANTS: Thirty-four patients (19 female, 15 male) whose age when diagnosed with retinoblastoma ranged from 1 to 72 months participated. Sixteen patients had unilateral retinoblastoma and 18 had bilateral retinoblastoma. INTERVENTION: Enucleation (3 bilateral, 31 unilateral) with implantation of a porous polyethylene (PP) sphere (16-20 mm in diameter) was performed. Of the 37 spheres, 34 were primary implants and 3 were secondary implants. In the eight patients with postimplantation exposure, the PP implant had to be removed. MAIN OUTCOME MEASURES: Data on eight sockets with exposed PP implant were measured. RESULTS: There were no implant extrusions, but conjunctival dehiscence-exposure occurred in eight patients (21.6%). In 3 of 37 sockets, the volume replacement was not good, and in 5 cases, fornices were too shallow to accommodate a well-fitting prosthesis. In all but one socket, the overall cosmesis was graded subjectively from acceptable (grade 2) to excellent (grade 3). CONCLUSIONS: Although the PP implant is a useful and a less-expensive alternative to hydroxyapatite in the porous matrix implant category, if conjunctival exposure takes place, the implant presents a serious management problem because of its nonresponsiveness to medical and surgical treatments.

Phacomorphic glaucoma associated with choroidal melanoma.

Patients with phacomorphic glaucoma present with mature cataract, shallowing of the anterior chamber, and angle-closure glaucoma. The opaque ocular media due to cataract formation usually precludes visualization of the posterior segment of the affected eyes. The authors describe a 65-year-old man who presented with reduced vision and clinical findings typical of phacomorphic glaucoma. Preoperative ultrasonography revealed an intraocular tumor, and magnetic resonance imaging showed a high signal intensity in T1-weighted images and a low signal intensity in T2-weighted images consistent with choroidal melanoma. Histopathologic examination of the tumor after enucleation confirmed the diagnosis. The clinical findings characteristic of phacomorphic glaucoma may be associated with choroidal melanoma. Ultrasonography or other imaging studies should be performed on eyes with phacomorphic glaucoma and opaque ocular media to allow timely detection of any mass lesion and to guide appropriate surgical management.

Cystic basal cell carcinoma of the orbit and eyelids.

When basal cell carcinoma develops cystic change, its clinical and radiological features vary, leading to confusion in differential diagnosis We report four cases with cystic formation of 62 patients with orbital and adnexal basal cell carcinoma encountered during the last 12 years. The salient clinical, radiological, and histopathological features of these cases are presented and differential diagnosis of large cystic lesions in the orbit is discussed. When the basal cell carcinoma develops cystic changes it mimics other orbital cysts, including inclusion cysts due to penetrating injury, mucoceles, and necrotic metastatic tumors.

Pharmacokinetics of azithromycin in trachoma patients: serum and tear levels.

OBJECTIVE: To determine the effectiveness of single-dose oral azithromycin in the treatment of Chlamydia trachomatis through monitoring of tear and serum levels. DESIGN: Nonrandomized, clinical trial. PARTICIPANTS: Fourteen school-age children with active trachoma (one failed to complete the study). INTERVENTION: A single dose of azithromycin (20 mg/kg) was administered orally to 14 patients, and tear and serum levels were determined with high-performance liquid chromatography at 12, 24, 48, 72, 96, 120, and 144 hours after administration. MAIN OUTCOME MEASURES: Azithromycin levels in tears and serum. RESULTS: Peak levels of 1.53 microg/ml (standard deviation [SD] +/- 0.94) and 0.15 microg/ml (SD +/- 0.04) were obtained at 12 hours in both tears and serum, gradually decreasing over 144 hours. All patients were disease-free by 6 months. CONCLUSIONS: Levels of azithromycin in patients with trachoma were found to be within minimum inhibitory concentration range for Chlamydia trachomatis (0.03-0.25 microg/ml) throughout the monitored period of 6 days.

Extrusion of porous polyethylene orbital implant in recurrent retinoblastoma.

High-density porous polyethylene allografts are used as orbital implants in reconstruction of anophthalmic sockets. The use of this material for integrated buried implants is rather new, and studies on removed implants from humans are limited. We studied the case of a 6-year-old boy with an extruded porous polyethylene implant due to orbital recurrence of retinoblastoma. The clinical and morphological features are reported. Histopathology revealed fibrovascular downgrowth in the outer two thirds of the sphere. Scanning electron microscopy, however, documented further downgrowth of fibrous tissue into the central core. Transmission electron microscopy depicted a spectrum of collagen fiber orientations to polyethylene material, ranging from perpendicular to concentric. Immunohistochemistry studies were inconclusive.

Orbital hemangiopericytoma: clinical and morphologic features.

PURPOSE: To report the clinical and histopathologic features of orbital hemangiopericytoma. METHOD: We review the clinical and histopathologic features in seven patients. RESULTS: Ultrasonography, computed tomography, and magnetic resonance imaging defined the location and extent of the tumor in each patient but did not disclose pathognomonic features for the specific diagnosis of hemangiopericytoma. The predominating histopathologic feature of each tumor was a mixed pattern of ovoid cells and sinusoidal space formations. Five patients showed mild to severe cellular atypia; three had obvious pleomorphism and increased number of abnormal mitotic figures. Tumor cells disclosed cytoplasmic reactivity for vimentin but in five cases were negative for other immunologic markers. Six patients received surgical treatment with an attempt for total removal of the tumor; one had biopsy and radiation therapy. In two patients, radiation therapy was given in addition to tumor removal with orbital exenterations. Three patients died with recurrent and metastatic disease, and four patients are alive without tumor for a follow-up period ranging from 3 to 9 years. CONCLUSIONS: Orbital hemangiopericytoma may behave as a malignant tumor, leading to local recurrence or metastasis, or both. Clinical and histopathologic findings should be considered jointly to evaluate the clinical course; histopathologic findings alone are not sufficient to predict the biologic behavior of this tumor.