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D M Moshfeghi

Publications and source records attributed to D M Moshfeghi.

17 recordsLinked to original sources
PubMed2001

Splice site mutation in the peripherin/RDS gene associated with pattern dystrophy of the retina.

PURPOSE: To report the phenotype and genotype of a splice site mutation at intron 2 of the peripherin/RDS gene in four half-siblings with pattern dystrophy of the retina. DESIGN: Experimental study. METHODS: In four siblings with a common mother and three separate fathers, complete ophthalmic examination, pedigree, electrophysiologic testing, and fluorescein angiography studies were obtained. Genomic DNA from serum lymphocytes was isolated and used as a template for primers specific for the cone homeobox gene (CRX), rhodopsin (RHO), and peripherin/RDS genes to conduct single stranded conformational analysis and cycle sequencing. RESULTS: The pedigree of four affected siblings suggested probable autosomal dominance transmission of pattern dystrophy. In the four siblings, best corrected visual acuity ranged from 20/20 to 20/80 by Snellen chart. Clinical findings included discrete, localized degenerative changes of the macular retinal pigment epithelium in all patients, with subclassification foveal. One patient exhibited pigment clumping within the atrophic areas. Another patient exhibited yellow flecks diffusely in the macula. Fluorescein angiographic findings included central hypofluorescence with a surrounding rim of hyperfluorescence that corresponded to the observed fundus lesions and window defects. There was a range of electroretinography (ERG) and electrooculography (EOG) findings. One patient demonstrated both cone and rod dysfunction on ERG testing and another demonstrated decreased rod function. EOG testing was normal in two patients and mildly diminished in one patient. DNA sequencing identified a point mutation in intron 2 of the peripherin/RDS gene, consisting of an A to T change at 1068+3, present in all four affected patients. CONCLUSIONS: Four siblings with pattern dystrophy of the retina presented a splice site mutation in the peripherin/RDS gene.

Adult↗
PubMed2001

Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of multiagent chemotherapy in the neoadjuvant treatment of retinoblastoma. DESIGN: Noncomparative, prospective case series. PARTICIPANTS: Twenty consecutive patients with multifocal intraocular retinoblastoma (4 unilateral, 16 bilateral [36 eyes]). INTERVENTION: Eight cycles of chemotherapy with carboplatin and vincristine were administered at 3-week intervals over a 6-month period. Supplemental therapy was withheld until disease progression was documented. MAIN OUTCOME MEASURES: Disease progression (defined as tumor growth, vitreous or subretinal seed progression, and new tumor formation), delay of external beam radiotherapy, and ocular survival. RESULTS: Thirty-six eyes were treated. Eighteen eyes had Reese-Ellsworth group I-III tumors, and 16 eyes had Reese-Ellsworth group IV-V tumors at diagnosis. Two patients, who had unilateral disease at diagnosis, subsequently had tumors develop in the contralateral eye. Nineteen of 20 patients (95%) completed eight cycles of chemotherapy without disease progression. Three eyes of three different patients were successfully treated with chemotherapy alone. Thirty-three of 36 eyes (92%) progressed after completion of chemotherapy: 15 of the 18 eyes (83.3%) with Reese-Ellsworth group I-III and 16 of 16 eyes (100%) with Reese-Ellsworth group IV-V tumors. Seventeen eyes (52%) had growth of a tumor, whereas 14 eyes (42%) had progressive vitreous seeding, and 2 eyes (6%) had new tumors develop. Fifteen eyes (42%) required external beam radiotherapy. Twenty-nine of 36 (80.5%) eyes were salvaged. The median follow-up after chemotherapy was 19 months (range, 3-42 months). CONCLUSIONS: Multiagent chemotherapy alone does not ensure a cure for multifocal intraocular retinoblastoma. Supplemental focal therapy is needed to control disease progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Retreatment effect of NPe6 photodynamic therapy on the normal primate macula.

PURPOSE: To evaluate the safety and efficacy of repeated photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6) on normal primate fovea and choroid. METHODS: Macaca fuscata monkeys were used as experimental subjects. Mono-L-aspartyl chlorin e6 at a dose of 2 mg/kg was administered by intravenous infusion. Laser irradiation was applied within 5 minutes using a 664-nm diode laser at a power output of 5.9 mW (750 mW/cm2), spot size of 1,000 microm, and time of 10 seconds. This resulted in a fluence of 7.5 J/cm2. Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea and posterior fundus near the arcade vessels of each eye. The animals were killed and the eyes were enucleated for histologic study 2 weeks after the last treatment. RESULTS: Limited changes could be observed in the sensory retina under light microscopy. Photoreceptor cells and outer segments were not damaged, even after repeated PDT. Proliferation and duplication of the retinal pigment epithelial cells were common findings. A plaque of fibrous tissue was present, interwoven with retinal pigment epithelial cells in eyes that received repeated PDT. The retinal vessels remained patent even after three sessions of PDT. However, occlusion of the choriocapillaris and the large choroidal vessels was observed after repeated PDT treatment. CONCLUSION: Repeated PDT of healthy nonhuman primate fundi using a hydrophilic photosensitizer (NPe6) shows preservation of the neurosensory retina components and architecture with damage confined to the retinal pigment epithelium and choriocapillaris.

Animals↗
PubMed2001

Photodynamic therapy of experimental choroidal neovascularization with a hydrophilic photosensitizer: mono-L-aspartyl chlorin e6.

PURPOSE: To demonstrate the selective localization of the hydrophilic photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in experimental choroidal neovascularization in nonhuman primate eyes. METHODS: Sixty-seven experimental choroidal neovascular lesions (CNV) were created in the fundi of Macaca monkeys using the modified Ryan's model and documented by fluorescein and indocyanine green angiography. To determine the biodistribution of NPe6 and the optimal timing of laser irradiation after dye administration, NPe6 angiography and fluorescence microscopy with NPe6 were performed. Photodynamic therapy (PDT) was performed at various dye doses (0.5-10.0 mg/kg) and laser fluences (7.5-225.0 J/cm2) on the CNV and on 10 areas of normal retina and choroid. Treatment outcomes were assessed by fluorescein and indocyanine green angiography and confirmed by light and electron microscopy. RESULTS: NPe6 fluorescence microscopy demonstrated intense fluorescence of CNV and retinal pigment epithelial cells. Choroidal vessel walls and outer retina adjacent to CNV fluoresced moderately; retinal vessel walls and microcapillaries had trace fluorescence. The fluorescence of CNV lesions on fluorescein angiography became stronger than that of retinal vessels 20-60 minutes after dye injection. Choroidal neovascular lesion closure was achieved with NPe6 PDT without significant damage to the sensory retina. Histology demonstrated necrosis of CNV endothelial cells with minimal damage to surrounding tissues. CONCLUSIONS: NPe6 PDT selectively localizes to experimental CNV in nonhuman primates, resulting in occlusion of CNV with sparing of the neurosensory retina.

Animals↗
PubMed2000

Problems with and pitfalls of photodynamic therapy.

OBJECTIVE: To delineate the various factors that may influence the outcome of photodynamic therapy of the retina and choroid. DESIGN: Experimental animal study. ANIMALS: Pigmented and nonpigmented rabbits; rhesus monkeys. INTERVENTION: The hydrophilic photosensitizer, mono-L-aspartyl chlorin e6, which is maximally activated at 664 nm, was studied after intravenous injection into pigmented and nonpigmented rabbits and rhesus monkeys. Laser light was supplied by a red diode laser coupled to a modified slit-lamp biomicroscope and delivered to the ocular fundus after passing through a standard fundus contact lens. Standard photodynamic parameters were used. The effects of fundus pigmentation, intraocular pressure, spot focus and defocus, region of fundus treated, equivalent fluence, and retreatment were observed in the different animal species. MAIN OUTCOME MEASURES: Slit-lamp biomicroscopy, fluorescein angiography, light and transmission electron microscopy. RESULTS: Fundus pigmentation appeared to be a factor only at the lowest fluence level tested, where only 4 of 12 lesions attempted in pigmented fundi were noted on fluorescein angiography, compared with 12 of 12 lesions in albino rabbits. At normal intraocular pressures and a given fluence, 10 of 10 lesions were fully manifested on fluorescein angiography, compared with 4 of 10 at 30 mmHg and 0 of 10 at pressures sufficient to blanch the optic nerve (>60 mmHg). For laser spots either focused or defocused, there were 6 of 6 lesions that were fully manifested on fluorescein angiography for each of the parameters. Lesions treated in the fovea resulted in larger spots on fluorescein angiography. The fluence of 5 mW for 10 seconds resulted in a larger lesion on angiography than the equivalent fluence of 10 mW for 5 seconds. Areas of retreatment in rabbits demonstrated more thinning of the neurosensory retina and loss of photoreceptor outer segments and nuclei than corresponding areas receiving one treatment. CONCLUSIONS: Photodynamic therapy results varied, depending on intraocular pressure, region of fundus treated, ocular pigmentation, and the total time of exposure to the photosensitizer. Retreatment resulted in progressive thinning of the neurosensory retina with loss of photoreceptor outer segments and nuclei in the rabbit eye.

Animals↗
PubMed2000

Mardi Gras eye injury survey, 1998-1999.

BACKGROUND: We studied the nature of associated ocular trauma during the 1998 and 1999 New Orleans parade seasons and whether trends were observable from previous surveys. METHODS: A prospective survey and retrospective analysis included 18 emergency rooms (ERs) in the New Orleans area. RESULTS: Sixteen surveys representing eight ERs were completed between February 19 and 24, 1998, and 32 surveys representing five ERs were completed between February 5 and 17, 1999. In both years, the most common ocular complaints were pain, blur, foreign body sensation, tearing, and photophobia. The most common slit lamp findings in 1998 were within normal limits, corneal abrasion, and conjunctival hyperemia. In 1999, the most common findings were subconjunctival hemorrhage, corneal abrasion, cell and flare, and lid laceration. CONCLUSIONS: Projectile injuries of the eyes are common during Mardi Gras due to the nature of interaction between paradegoers and float riders. We found no identifiable trend in the number or type of injuries reported in 1986, 1987, and 1998 Mardi Gras surveys.

Adult↗
PubMed1999

Angiographic and histologic effects of fundus photodynamic therapy with a hydrophilic sensitizer (mono-L-aspartyl chlorin e6).

PURPOSE: To demonstrate the efficacy of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in closing choroidal vessels at low energy levels, that tissue uptake and clearance are rapid, and that low concentrations of drug are needed to achieve clinical effects. DESIGN: Experimental animal study. ANIMALS: Pigmented rabbits and Japanese monkeys were used in this study. METHODS: Using a modified 664-nm diode laser, the fundi of pigmented rabbits and Japanese monkeys were irradiated after intravenous administration of NPe6 (2-100 mg/kg). Time from injection to irradiation varied from 5 to 15 minutes, and duration of exposure varied from 1 to 10 seconds. Power output at the corneal surface was either 3.6 or 5.9 mW. Animals were examined by indirect ophthalmoscopy and fluorescein angiography at 2 hours and 7 days after treatment. After enucleation 7 days after treatment, specimens were prepared for light and electron microscopy. MAIN OUTCOME MEASURES: Angiographic evidence of occlusion and histopathologic evidence of retinal damage. RESULTS: Both clinical and histopathologic examination demonstrated effects on the choroidal vasculature and the retinal pigment epithelium, including necrosis of endothelial cells and occlusion in choroidal vessels, particularly within the choriocapillaris, at low energy levels. Overlying neurosensory retina was minimally affected. Fluorescein angiography of lesions treated with 2 mg/kg and laser fluence of 2.3 to 7.5 J/cm2 showed a normal appearance 2 hours after treatment, which changed to early hypofluorescent and later hyperfluorescent lesions 7 days after treatment. In contrast, those animals receiving the 10-mg/kg dose and laser fluence of 0.46 to 0.75 J/cm2 showed marked hypofluorescence of choroidal lesions and occlusion of retinal vessels 7 days after treatment. CONCLUSIONS: Effective occlusion of normal choroidal vessels was achieved at 2 mg/kg using 2.3 to 7.5 J/cm2 or at 10 mg/kg using 0.46 to 0.75 J/cm2 with minimal injury to overlying neurosensory retina.

Animals↗
PubMed1998

Ocular vascular thrombosis following tin ethyl etiopurpurin (SnET2) photodynamic therapy: time dependencies.

BACKGROUND AND OBJECTIVES: To evaluate the optimal time from the end of photosensitizer injection to the commencement of light application for creating characteristic fundus lesions and the time to vascular occlusion following photodynamic therapy (PDT) with tin ethyl etiopurpurin (SnET2). MATERIALS AND METHODS: Following intravenous injection of SnET2 0.5 mg/kg or lipid emulsion alone, the fundus of rabbits was irradiated at different times (5 to 240 minutes) after photosensitizer injection using 664 +/- 7-nm laser light with an irradiance of 354 mW/cm2 and fluence of 20 J/cm2. Ophthalmoscopy and fluorescein angiography were performed 1 day after SnET2 PDT. In separate groups of rabbits, treated areas of the fundus were imaged within 30 minutes following PDT using fluorescein vesicle and microsphere angiography with scanning laser ophthalmoscopy to document time of vascular occlusion. All animals were killed 1 day following treatment and eyes were examined by histopathology. RESULTS: Areas of hypofluorescence (indicating vascular occlusion) were seen when activating laser light was applied 5 to 20 minutes after SnET2 injection. Retinal vessels remained perfused in all cases. The time to vascular occlusion was 70 to 120 and 40 to 90 minutes in nonpigmented and pigmented rabbits, respectively. No safety issues were seen. CONCLUSION: PDT with SnET2 was effective in occluding the choriocapillaris. Activating light needs to be applied within a specific time frame after photosensitizer injection to achieve vascular occlusion.

Animals↗
PubMed1997

Photodynamic therapy for choriocapillaris using tin ethyl etiopurpurin (SnET2).

BACKGROUND AND OBJECTIVE: To investigate the use of photodynamic therapy (PDT) using tin ethyl etiopurpurin (SnET2) for occluding the choriocapillaris in the eyes of pigmented rabbits. MATERIALS AND METHODS: Following intravenous injection of SnET2 (0.5 and 1 mg/kg) or lipid emulsion alone, the fundus of pigmented rabbits (n = 21) was irradiated starting 15 to 45 minutes after photosensitizer injection using 664-nm light at a fluence of 300 mW/cm2 and light doses of 5 to 20 J/cm2. Funduscopy, fluorescein angiography, and light and electron microscopy were performed at 1, 14, and 28 days after PDT. RESULTS: Following SnET2 and PDT, closure of the choriocapillaris was achieved with light doses as low as 5 J/cm2 (17 seconds) and a drug dose of 0.5 mg/kg of SnET2. Vascular occlusion was documented by fluorescein angiography and histology. Photodynamic damage was noted in the choriocapillary endothelial cells. Retinal pigment epithelial damage and outer retinal damage were also observed. No funduscopic, angiographic, or histologic findings were present in the eyes of pigmented control rabbits. CONCLUSIONS: PDT with SnET2 was effective in this animal model, using low levels of activating light for the occlusion of the choriocapillaris. This has clinical implications for the treatment of choroidal neovascularization and could be a more selective therapy than thermal laser photocoagulation.

Animals↗
PubMed1996

Fluorescent vesicle angiography with sodium fluorescein and indocyanine green.

BACKGROUND AND OBJECTIVE: The authors evaluated the feasibility of merging free-dye angiography and the fluorescent vesicle technique to achieve the best characteristics of both. MATERIALS AND METHODS: Fluorescent vesicles encapsulated with either indocyanine green or carboxyfluorescein were mixed with free indocyanine green or free sodium fluorescein, respectively, and imaged with a scanning laser ophthalmoscope in both an in vitro model and primate and rabbit models. RESULTS: In the in vitro model of the sodium fluorescein combination, optimal viewing of vesicleen capsulated dye and free dye was at a ratio of 150:1; for indocyanine green, the ratio was 50:1. In vivo, high-quality fluorescent vesicle angiograms were obtained that demonstrated leakage of free dye from choroidal laser spots. CONCLUSIONS: Free dye and fluorescent vesicles can be combined to obtain an angiogram with all of the advantages of a traditional angiogram, while allowing the operator to assess the changes in retinal or choroidal circulation directly.

Animals↗
PubMed1991

Microwave cyclodestruction for glaucoma in a rabbit model.

Microwave thermotherapy was used to treat experimentally induced glaucoma. Microwave-induced cyclodestruction was successful in reducing intraocular pressure in all treated glaucomatous eyes for 4 weeks. Two additional glaucomatous eyes were left untreated to serve as controls, and were noted to have persistently elevated intraocular pressures. Six additional eyes were then subjected to an equivalent treatment (50 degrees C in five 1-minute applications), which resulted in approximately 180 degrees of heat treatment just posterior to the corneoscleral limbus. These specimens were evaluated with light microscopy at baseline, 24 hours, and 7 days after treatment. Our clinical and histopathologic evaluations suggested that microwave thermotherapy (delivered under thermometry control) allowed for chorioretinal/ciliary body destruction that resulted in reductions of intraocular pressure in glaucomatous eyes.

Animals↗
PubMed1991

Palladium 103 ophthalmic plaque radiotherapy.

We compared the ocular radiation distribution of palladium 103 (103Pd) vs iodine 125 (125I) ophthalmic plaques sewn to 12 human donor eyes. We then performed preoperative comparative simulations on the first seven patients to be treated with palladium 103 plaque therapy for choroidal melanoma. The in vitro experiment involved palladium 103 seeds placed into a Silastic seed holder, which was affixed into standard 14-mm gold eye plaques. Then the plaques were sewn onto 12 human donor eyes so as to approximate either the nasal (six eyes) or temporal (six eyes) equator. Three sets of two thermoluminescent dosimeters were used to quantify the amount of radiation delivered by the episcleral plaques. Thermoluminescent dosimeters were sewn to the sclera in three locations: on the center of the cornea, on the sclera beneath the macula, and at the equator in a position opposite the plaque. This experiment was then repeated with iodine 125 seeds and thermoluminescent dosimeters. After the plaques were adjusted to equalize their activity (plaque strength), the palladium 103 plaques were found to deliver less radiation to the three target points. Comparative clinical dosimetry also reflected this difference. Preoperative simulations comparing equal doses to the tumors' apex revealed that the palladium 103 ophthalmic plaques delivered more radiation to the tumor and less radiation to most normal ocular structures.

Brachytherapy↗
PubMedDate not supplied

Noninvasive monitoring of intraocular pharmacokinetics of daunorubicin using fluorophotometry.

PURPOSE: Daunorubicin is a cytotoxic drug, which, in nontoxic doses, is effective in preventing cellular proliferation in experimental vitreoretinopathy. We studied dose and clearance of daunorubicin in various ocular tissues using fluorophotometry techniques. METHODS: In vitro tests: The emission of fluorescence from the daunorubicin solution having a concentration range of 0.1 to 10 micrograms/mL in phosphate buffer was measured using an excitation wavelength range of 489 +/- 10 nm. The emission of fluorescence was measured at 514 nm; the linearity of the response was determined using linear regression analysis. There is a fluorescence peak of daunorubicin at 485 nm. The validity and reproducibility of the method were examined. In vivo tests: The rabbits were randomized into three groups and daunorubicin concentrations of 4, 6, or 8 micrograms/mL were injected into the vitreous. Fluorophotometry scanning from the retina to the anterior chamber was performed with a commercially available fluorophotometer at various times up to 48 hours after injection to quantify fluorescence emission of daunorubicin. RESULTS: The standard curve of fluorescence versus concentration of daunorubicin was linear in the range of 0.1 to 8 micrograms/mL. It was sensitive up to 0.1 microgram. The daunorubicin time concentration profile showed a dose response relationship over the 48-hour period studied. The half-life of daunorubicin in the vitreous was about 5 hours. CONCLUSION: We performed fluorophotometry using a fluorophotometer whose exciter emits light at 489 nm, which is very close to an absorption peak of daunorubicin. These two values are close enough to obviate the need for modifying the commercial fluorophotometer. Therefore the concentration of daunorubicin in the vitreous cavity can be measured noninvasively.

Absorption↗
PubMedDate not supplied

Enucleation.

The three most common indications for enucleation are intraocular malignancy, trauma, and a blind, painful eye. Recommending enucleation is one of the most difficult therapeutic decisions in ophthalmology. In some cases of malignancy, cryotherapy, laser photocoagulation, diathermy, chemotherapy, and radiation therapy may be viable alternatives to surgery. When surgery is chosen, evisceration or exenteration may be alternatives to enucleation. Once the decision is made to perform enucleation or evisceration, the surgeon must choose from several types of implants and wrapping materials. These devices can be synthetic, autologous, or eye-banked tissues. With certain implants, the surgeon must decide when and if to drill for subsequent peg placement. In this review, the authors discuss choices, techniques, complications, and patient consent and follow-up before, during, and after enucleation. Controversies and results of the Controlled Ocular Melanoma Study are summarized.

Eye Enucleation↗
PubMedDate not supplied

Toxicity of the photosensitizer NPe6 following intravitreal injection.

BACKGROUND AND OBJECTIVE: To determine the retinal toxicity of mono-L-aspartyl chlorin e6 (NPe6) following intravitreal injection. METHODS: Twelve Dutch-belted rabbits divided into 5 experimental groups (n=2 each) were injected intravitreally with 6.25, 12.5, 25, 50, or 100 microg of NPe6; one control group (n=2) was injected with intravitreal normal saline. One eye in each rabbit was sutured shut to test the effect of light exposure. Fundus photography and electroretinograms were performed before treatment and 2 days, 1 week, and 2 weeks after injection. Animals were euthanized and the eyes enucleated for histopathologic analysis. RESULTS: After 1 week, 4 uncovered eyes given 50 and 100 microg had central retinal vein occlusion and varying degrees of retinal hemorrhage. RPE proliferation was seen in the covered eyes given 50 or 100 microg. Electroretinograms revealed absent retinal response at 100 microg and mild toxicity at 50 microg, but no change from normal at doses of < or = 25 microg of NPe6. CONCLUSIONS: Intravitreal doses of < or = 25 microg NPe6 caused little or no apparent toxicity; however, toxicity was significant at doses of 50 microg and 100 microg.

Animals↗