Biomedical subjects
D Sarraf
Publications and source records attributed to D Sarraf.
Familial cavernous hemangioma: An expanding ocular spectrum.
OBJECTIVE: To describe the clinical and genetic findings in a family with multiple cases of cavernous hemangiomas. DESIGN: Investigational clinical and genetic study in which 3 generations of a family consisting of 12 members were screened with magnetic resonance brain imaging, dilated ophthalmoscopic examination, and cutaneous survey coupled with linkage analysis to determine affected individuals and to better define manifestations of this neuro-oculo-cutaneous syndrome. RESULTS: The proband had multiple cerebral cavernous hemangiomas and a choroidal hemangioma. Her son was found to harbor a retinal cavernous hemangioma. The proband's sister manifested a cerebral cavernous hemangioma, cutaneous hemangiomas, and a presumed choroidal hemangioma; her daughter demonstrated radiological findings suggestive of a cerebral cavernous hemangioma. The father of the proband demonstrated multiple, cutaneous hemangiomas. The remaining family members were free of lesions. The 7q locus could not be excluded as harboring the causative gene. CONCLUSIONS: This family may have a dominantly inherited neuro-oculo-cutaneous condition of cavernous hemangiomas with variable expressivity. The presence of choroidal hemangiomas in this phacomatosis has not been described previously to our knowledge. CLINICAL RELEVANCE: The presence of either retinal cavernous or choroidal hemangioma should alert the physician to search for features suggestive of systemic and familial involvement; either lesion may constitute the ocular component of the neuro-oculo-cutaneous phacomatosis, sometimes referred to as cavernoma multiplex. Arch Ophthalmol. 2000;118:969-973
Long-term drusen study.
PURPOSE: To determine the yearly incidence of visual loss in the fellow eyes of patients with unilateral neovascular age-related macular degeneration (ARMD) and to assess the drusen characteristics portending the greatest risk for this outcome. METHODS: A total of 101 patients with unilateral exudative ARMD and drusen only in the fellow eye were entered into the study and prospectively followed up to 9 years. Visual acuity, color fundus photography, fluorescein angiography, and grading of drusen characteristics were obtained for each patient on entry into the study. Patients were followed at annual intervals with color fundus photography. The study endpoint was the development of choroidal neovascularization (CNV) or geographic atrophy (GA) in the fellow eye. RESULTS: Yearly incidence rates for the development of an endpoint lesion were between 5 and 14%. The risk of CNV peaked at 4 years and dissipated thereafter. Longer follow-up was associated with a slightly increased incidence of GA. Greater drusen number was most highly associated with the development of an endpoint lesion. Drusen size and confluence were also significant. CONCLUSIONS: The risk of CNV in patients with ARMD is heralded by an increase in the number, size, and confluence of drusen. This risk eventually declines and is followed by later increased risk of GA.
AIDS and the eyes.
The eye is affected in 50-75% of adult AIDS patients. This rate of ocular involvement is much higher than that in symptom-free HIV-seropositive patients, and seems to increase in incidence with severity of disease. These observations indicate that regular screening of HIV-positive patients is warranted to allow early identification of potential vision and life threatening disease.
The role of iontophoresis in ocular drug delivery.
Iontophoresis has been utilized in the field of ophthalmology for many years. Present application of this technique has diminished considerably and few clinicians are currently familiar with its use. This review aims to educate the reader regarding the essential features of this procedure and to discuss the past and future role of iontophoresis in ocular drug delivery.
Involvement of the eyebrow fat pad in Graves' orbitopathy.
Involvement of the eyebrow fat pad in Graves' disease has never been reported. We noted that Graves' orbitopathy patients had bulkier eyebrows due to a larger eyebrow fat pad not associated with the preaponeurotic fat. A cadaver model was used to show that the eyebrow fat could be identified with magnetic resonance imaging (MRI) scans. Then, a series of Graves' orbitopathy patients were sent for orbital MRI scans, and the eyebrow fat was measured with maximum lengths and widths. The averages were compared to two groups of patients, one without orbital pathology, and one with orbital pathology causing proptosis but not due to Graves' disease. Graves' patients with early orbitopathy and incipient optic neuropathy or congestive orbits where optic neuropathy had to be ruled out had statistically significant larger eyebrow fat pads than either comparison group. This has clinical significance: The eyebrow fat may need to be debulked during operations such as blepharoplasty. Furthermore, periorbital fat may play a larger role in the disease process than previously thought.
Transscleral iontophoresis of foscarnet.
Current local treatments of cytomegalovirus retinopathy may result in serious intraocular complications. Using an animal model, we investigated transscleral iontophoresis as a technique for delivery of foscarnet to the vitreous. Using a probe tip surface area of 0.19 mm2, a current of 1 mA, and a duration of ten minutes, transscleral iontophoresis of 0.5 ml of a 24-mg/ml foscarnet solution was administered to 72 normal rabbits. Vitreous aspiration was performed at 12 intervals (15 minutes, 30 minutes, and one, two, four, eight, 16, 24, 32, 40, 48, and 60 hours) after iontophoresis, and samples were analyzed by high-performance liquid chromatography to determine the vitreous pharmacokinetics of foscarnet. A peak foscarnet concentration of 200 +/- 31 microM (mean +/- standard deviation) was attained four hours after iontophoresis and was well below the concentration reported to cause retinal toxicity. Therapeutic levels were maintained until 60 hours after iontophoresis. The elimination half-life was approximately 24 hours. No toxic effects to anterior chamber structures were observed by biomicroscopy. Transscleral iontophoresis of foscarnet may provide an effective and safe technique for local treatment of cytomegalovirus retinopathy in patients with acquired immunodeficiency syndrome.
Aqueous and vitreous concentration of mitomycin C by topical administration after glaucoma filtration surgery in rabbits.
PURPOSE: The authors investigated the aqueous and vitreous pharmacokinetics of mitomycin after postoperative topical administration in rabbits. METHODS: Filtration surgery was performed in one eye of each rabbit. On the first postoperative day, mitomycin solution (0.4 mg/ml) was administered by either topical drop or cellulose sponge in both eyes of each rabbit. Aqueous and vitreous paracenteses were performed at 0.25, 0.5, 1, 2, 3, and 4 hours thereafter. Three rabbits were tested at each time interval for each type of administration. RESULTS: After topical drop administration, the peak aqueous concentration was 0.03 +/- 0.02 microgram/ml (mean +/- standard error) in surgical eyes and 0.06 +/- 0.03 microgram/ml in control eyes. After sponge administration, the peak aqueous concentration was 0.10 +/- 0.03 microgram/ml in surgical eyes and 0.08 +/- 0.04 microgram/ml in control eyes. Peak aqueous concentrations from drop and sponge applications were achieved at 1 to 2 hours after administration. Vitreous levels were well below the concentration known to cause retinal toxicity at all time intervals tested. CONCLUSION: Postoperative topical administration of mitomycin was successful in delivering mitomycin into the aqueous humor of rabbit eyes. Alternative methods of mitomycin application from the currently popular intraoperative administration may be beneficial in situations in which mitomycin delivery across intact conjunctiva may be desirable.
Iontophoresis of reactive black 5 for pulsed dye laser sclerostomy.
Ab interno pulsed dye laser sclerostomy uses a gonioscopic approach to form a limbal fistula for the treatment of glaucoma. This procedure requires a full thickness penetration of stain in sclera for adequate absorption of the visible light energy. Iontophoresis is a technique using an electrical current to noninvasively deliver Reactive Black 5 (RB5) stain into sclera. This project determined the stability of RB5 stain as well as the optimal parameters for iontophoresis (probe tip surface area, current, and duration) in a rabbit model. RB5 stain was stable over time (72 hr) as well as after exposure to extreme heat (120 degrees C), scleral constituents (namely collagen), high concentrations of oxidants (1.5% H2O2), and laser light energy. Ideal parameters for iontophoresis included a probe tip surface area between 0.1 and 0.7 mm2, a current of 0.5 mA, and a duration of 5 min. The maximum concentration of RB5 stain achieved in sclera was 0.15%. The threshold of ablation for RB5 using an energy of 250 mJ was 0.001%. Iontophoresis can effectively deliver RB5 stain into sclera and may be a viable adjunct to ab interno pulsed dye laser sclerostomy procedures in the eye.
Iontophoresis of methylene blue for gonioscopic pulsed dye laser sclerostomy.
Iontophoresis of methylene blue using pipette tip probes is an effective means of scleral staining in preparation for gonioscopic pulsed dye laser sclerostomy. The effects of the surface area of the pipette tip and of the duration of iontophoresis on the concentration and distribution of stain were investigated in rabbit eyes. Iontophoresis of 1% methylene blue was done using currents from 0.2 to 2.0 mAmp, pipette tip probes with surface areas from 0.02 to 7.1 mm2, and durations of iontophoresis from 0.5 to 10 minutes. Optimum iontophoresis parameters for delivering methylene blue to the eye were a current of 0.4 mA, a probe tip surface area of 0.19 mm2, and a duration of five minutes. The maximal scleral stain concentration, approximately 0.4%, was achieved using these optimal parameters. Microscopic analysis of frozen tissue sections demonstrated the stain to have penetrated the full thickness of the sclera after five minutes. Tissue samples were analyzed for dye 0.5, 2, 5, 12, and 24 hours after iontophoresis was completed. Decreased dye concentration by over 50% within 2 hours and complete disappearance of dye within 24 hours were demonstrated. Methylene blue concentration thresholds for laser ablation were also examined; the threshold of ablation of methylene blue was 0.0625% when an energy level of 75 mJ was used. We propose that iontophoresis of methylene blue is a useful adjunct to pulsed dye laser sclerostomy formation.
Lymphocytotoxins in vasculitis. Correlation with clinical manifestations and laboratory variables.
Twenty-eight of 53 patients with various types of vasculitis were found to have cold reacting lymphocytotoxins (LCT). LCT were cytotoxic to both peripheral blood B and T cells as well as to OKT4 and OKT8 subpopulations. The interaction with the B cells was more pronounced than with the T cells as shown by reactivity with the former at higher serum dilutions than with the latter. Similar results were obtained with eluates from the unseparated lymphocytes and from B or from T cells. Partial purification of LCT demonstrated that they belong to the IgM class. LCT correlated with the level of circulating immune complexes as determined by the fluid phase C1q binding assay, but they did not correlate with the level of immunoglobulins, complement or antinuclear factors. The presence of LCT correlated significantly with the activity but not with the disease duration or the number of involved organs. Correlation of LCT with the activity of vasculitis implies that these cytotoxins may have a pathogenetic role and perhaps may serve as a marker for disease activity.