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Biomedical subjects

D T Azar

Publications and source records attributed to D T Azar.

At least 37 records · Page 2Linked to original sources
PubMed2001

Survey of patients with granular, lattice, avellino, and Reis-Bücklers corneal dystrophies for mutations in the BIGH3 and gelsolin genes.

OBJECTIVES: To search for novel mutations that cause corneal stromal dystrophies and to confirm or revise the clinical diagnosis of patients with these mutations. PATIENTS: Through review of the records of the Cogan Eye Pathology Laboratory at the Massachusetts Eye and Ear Infirmary, Boston, and of clinical records, we ascertained 14 unrelated patients with the clinical or histopathologic diagnosis of granular (3 cases), Avellino (5 cases), lattice (5 cases), or Reis-Bücklers (1 case) corneal dystrophy. METHODS: Clinical records and histopathologic findings of the index patients and their relatives were reviewed. Patients and selected relatives donated a blood sample from which leukocyte DNA was purified and assayed for mutations in the BIGH3 gene and, in 2 patients, the gelsolin gene, using the polymerase chain reaction and direct genomic sequencing. RESULTS: All index patients with the diagnosis of granular dystrophy or Avellino dystrophy had the missense mutation Arg555Trp or Arg124His, respectively, previously reported in the BIGH3 gene. Of the 5 index patients with a prior diagnosis of lattice dystrophy, 2 had the originally reported lattice mutation (Arg124Cys) in the BIGH3 gene, 1 had a more recently reported missense mutation (His626Arg) in the same gene, 1 had the missense mutation Asp187Asn in the gelsolin gene, and 1 had no detected mutation in either gene. Affected members of the family with Reis-Bücklers dystrophy did not carry the previously reported mutations Arg555Gln or Arg124Leu but instead carried a novel missense mutation Gly623Asp in the BIGH3 gene. CONCLUSIONS: Molecular genetic analysis can improve the accuracy of diagnosis of patients with corneal dystrophies. Two patients with a prior diagnosis of lattice corneal dystrophy had their diagnosis changed to gelsolin-related amyloidosis (1 case) or secondary, nonhereditary localized amyloidosis (1 case). A novel mutation in the BIGH3 gene that causes Reis-Bücklers dystrophy was uncovered through this analysis, and another recently reported novel mutation was encountered. These findings serve to expand our knowledge of the spectrum of pathogenic mutations in BIGH3.

Adult↗
PubMed2001

Determination of corneal asphericity after myopia surgery with the excimer laser: a mathematical model.

PURPOSE: To determine the theoretical change of corneal asphericity within the zone of laser ablation after a conventional myopia treatment, which conforms to Munnerlyn's paraxial formula and in which the initial corneal asphericity is not taken into consideration. METHODS: The preoperative corneal shape in cross section was modeled as a conic section of apical radius R(1) and shape factor p(1). A myopia treatment was simulated, and the equation of the postoperative corneal section within the optical zone was calculated by subtracting the ablation profile conforming to a general equation published by Munnerlyn et al. The apical radius of curvature r(2) of the postoperative profile was calculated analytically. The postoperative corneal shape was fitted by a conic section, with an apical radius equal to r(2) and a shape factor p(2) equal to the value that induced the lowest sum of horizontal residuals and the lowest sum of squared residuals. These calculations were repeated for a range of different dioptric treatments, initial shape factor values, and radii of curvature to determine the change of corneal asphericity within the optical zone of treatment. RESULTS: Analytical calculation of r(2) showed it to be independent of the initial preoperative shape factor p(1). The determination of p(2) was unambiguous, because the same value induced both the lowest sum of residuals and the lowest sum of the squared residuals. For corneas initially prolate (p(1) < 1), prolateness increased (p(2) < p(1) < 1), whereas for oblate corneas (p(1) > 1), oblateness increased (p(2) > p(1) > 1) within the treated zone after myopia treatment. This trend increased with the increasing magnitude of treatment and decreased with increasing initial apical radius of curvature R(1). CONCLUSIONS: After conventional myopic excimer laser treatment conforming to Munnerlyn's paraxial formula, the postoperative theoretical corneal asphericity can be accurately approximated by a best-fit conic section. For initially prolate corneas, there is a discrepancy between the clinically reported topographic trend to oblateness after excimer laser surgery for myopia and the results of these theoretical calculations.

Cornea↗
PubMed2001

Matrilysin cleavage of corneal collagen type XVIII NC1 domain and generation of a 28-kDa fragment.

PURPOSE: To localize endostatin and collagen type XVIII in human corneas and to characterize the enzymatic action of matrix metalloproteinases (MMPs) in the cleavage of collagen type XVIII and generation of endostatin in the cornea. METHODS: Anti-endostatin and anti-hinge antibodies were generated using peptide fragments corresponding to the endostatin region and the adjacent nonendostatin hinge region of collagen XVIII noncollagenous (NC)1 domain, respectively. Confocal immunostaining was performed to localize collagen XVIII in human corneas. SV40-immortalized corneal epithelial cells were immunoprecipitated and incubated with active MMP-1, -2, -3, -7, or -9, and Western blot analysis was performed to study collagen XVIII cleavage. Incubation with MMP-7 was performed at various concentrations (0, 2, 4, and 6 microg/ml) and time intervals (0, 1, 5, and 12 hours). Purified recombinant NC1 fragment of collagen XVIII was also digested with MMP-7, and the cleavage product was sequenced. RESULTS: Collagen XVIII was immunolocalized to the human corneal epithelium, epithelial basement membrane, and Descemet membrane. Western blot analysis demonstrated a 180- to 200-kDa band corresponding to collagen XVIII. MMP-7 (but not MMP-1, -2, -3, and -9) cleaved corneal epithelium-derived collagen XVIII to generate a 28-kDa endostatin-spanning fragment in a time- and concentration-dependent fashion. MMP-7 cleaved purified recombinant 34-kDa NC1 fragment of collagen XVIII in the hinge region to generate a 28-kDa fragment. CONCLUSIONS: Collagen XVIII is present in human cornea. MMP-7 cleaves the collagen XVIII NC1 domain to generate a 28-kDa fragment in the cornea.

Amino Acid Sequence↗
PubMed2000

A new surgical technique of microkeratome-assisted deep lamellar keratoplasty with a hinged flap.

We describe a new surgical technique of microkeratome-assisted deep lamellar keratoplasty for treating patients with corneal stromal disease and normal endothelium. A microkeratome is used to create a hinged anterior stromal flap in the host cornea, and the diseased stroma is resected or ablated. A complementary donor stromal button, prepared using a microkeratome and an artificial anterior chamber, is transplanted prior to repositioning of the flap. The flap may be lifted at a later date, and an excimer laser used to correct residual refractive errors. Notwithstanding the preliminary and theoretical nature of this report, this technique may improve the outcomes of deep lamellar keratoplasty and may allow for decreased postoperative complications. Arch Ophthalmol. 2000;118:1112-1115

Corneal Diseases↗
PubMed2000

Late traumatic dislocation of laser in situ keratomileusis corneal flaps.

PURPOSE: To report the management and outcome of late-onset traumatic dislocation of laser in situ keratomileusis (LASIK) flaps. DESIGN: Retrospective, observational case series. PARTICIPANTS: Four patients with late-onset LASIK flap dislocation occurring after mechanical trauma at various intervals (10 days-2 months) after the procedure. INTERVENTION: In all cases of postoperative traumatic LASIK flap dislocation, the flap was refloated with scraping and irrigation of the underlying stromal bed within 12 hours of the injury. A bandage contact lens was placed, and a regimen including topical antibiotics and corticosteroids was instituted in all cases. MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity and complications associated with the surgery were monitored. RESULTS: Postoperative follow-up ranged from 4 to 21 months. Nonprogressive epithelial ingrowth was noted in one patient and diffuse lamellar keratitis developed in another patient. All patients recovered pretrauma spectacle-corrected visual acuity. CONCLUSIONS: Corneal LASIK flaps are prone to mechanical dislocation as late as 2 months after the procedure. Appropriate management results in recovery of optimal visual outcomes.

Adult↗
PubMed2000

Theoretical analysis of ablation depths and profiles in laser in situ keratomileusis for compound hyperopic and mixed astigmatism.

PURPOSE: To compare the theoretical ablation depths and profiles of 4 treatment strategies for compound hyperopic and mixed astigmatism. SETTING: Theoretical analysis. METHODS: Corneal contour drawings of theoretical corneal ablation profiles during laser in situ keratomileusis (LASIK) and photoastigmatic refractive keratectomy were made. The depths of tissue ablation in 4 treatment strategies for compound hyperopic astigmatism (Groups 1 to 4) and for mixed astigmatism (Groups 5 to 8) were compared: (1) combined hyperopic spherical and myopic cylindrical treatments (Groups 1 and 5); (2) combined spherical and hyperopic cylindrical treatments (Groups 2 and 6); (3) combined cylindrical treatments (Groups 3 and 7); (4) combined cross-cylinder and spherical equivalent treatments (Groups 4 and 8). RESULTS: In compound hyperopic astigmatism, the 4 approaches resulted in identical final curvatures, but the ablation depths were greatest in Group 1 (combined hyperopic spherical and myopic cylindrical treatments). The smallest amount of ablation occurred in Group 2 (combined hyperopic spherical and hyperopic cylindrical treatments) and Group 3 (combined hyperopic cylindrical treatments), which had similar tissue ablation patterns. In mixed astigmatism, the greatest ablation depth was in Group 5, followed by Group 8, and Groups 6 and 7. The tissue ablation depths and profiles were similar in Groups 6 and 7. CONCLUSION: The treatment approaches in Groups 2, 3, 6, and 7 (which avoided the use of minus cylinder) resulted in the smallest degree of stromal ablation. Patients with compound hyperopic or mixed astigmatism may benefit from reduced ablation depths by deferring treatment until hyperopic cylindrical and/or combined cylindrical treatments are available.

Astigmatism↗
PubMed2000

Outcome of corneal and laser astigmatic axis alignment in photoastigmatic refractive keratectomy.

PURPOSE: To compare the refractive results of laser astigmatic treatment in eyes in which the astigmatic axes of the eye and laser are aligned by limbal marking at the 6 o'clock position and in eyes that are not marked. SETTING: University Hospital and Clinics, Madison, Wisconsin, USA. METHODS: This retrospective study comprised 143 eyes that had photoastigmatic refractive keratectomy with the VISX Star excimer laser. The eyes were divided into marked (G1) and unmarked (G2) groups. Based on the preoperative astigmatism, each group was subdivided into low astigmatism (</=1.00 diopter [D]) and high astigmatism (>/=1.25 D). Early postoperative manifest refractions (1.0 to 2.5 months) were analyzed. The Alpins vector analysis method was used to calculate the target induced astigmatism, surgically induced astigmatism, difference vector (DV), magnitude of error (ME), angle of error (AE), and index of success (IS). RESULTS: There was no significant difference between the groups in DV, ME, and IS. When the subgroups were analyzed, the DV and ME were comparable; the IS in the G1 high astigmatism subgroup was significantly better than that in the G2 high astigmatism subgroup (0.22 +/- 0.08 and 0.29 +/- 0.04, respectively; P <.0001). There was comparable scatter of AE values; 30% and 36% in G1 and G2, respectively, had an AE of 0. Similar scatter was observed in the subgroups. Of the eyes that had an AE of 0, 90% and 43% in the high astigmatism subgroups of G1 and G2, respectively (P <.05), had full correction of astigmatism. CONCLUSION: Limbal marking and subsequent eye and laser astigmatic axis alignment improved the refractive outcome of laser astigmatic treatment of >/=1.25 D. A preliminary report of an ongoing prospective randomized study of eyes that had laser in situ keratomileusis is included.

Adult↗
PubMed2000

Differential expression of MT1-MMP (MMP-14) and collagenase III (MMP-13) genes in normal and wounded rat corneas.

PURPOSE: Several members of the matrix metalloproteinase (MMP) group have been identified in the rat cornea during corneal wound healing. The aim of the present study was to identify additional members of the MMP gene family in the rat cornea and localize the expression of membrane type-1 matrix metalloproteinase (MT1-MMP; MMP-14) and collagenase III (MMP-13) in normal and wounded corneas. METHODS: Adult rats underwent laser keratectomy on the right eye. Unwounded left eyes were normal controls. Corneas were collected and processed at different times post-wounding. Reverse transcription-polymerase chain reaction (RT-PCR) and DNA sequencing were used to discover the MMP genes expressed in the corneas. In situ hybridization was performed to localize the mRNA expression of MMP-14 and MMP-13. RESULTS: MMP-13 mRNA was detected in epithelial cells of wounded corneas, but not in normal controls; MMP-14 was found in both normal and wounded corneas. MMP-14 mRNA was expressed predominantly in the stromal keratocytes and rarely in the basal epithelial cells in normal and wounded corneas. MMP-13 mRNA was localized exclusively to basal cells of the epithelium at the wounded area from 6 hours to 3 days after wounding. CONCLUSIONS: MMP-14 and MMP-13 expression in rat corneas parallels that of gelatinases A and B, respectively. MMP-13 may play an important role in the gelatinase B-associated proteolytic cascade that allows rapid turnover of the extracellular matrix (ECM) components during corneal wound healing. MMP-14 may contribute to removing abnormal ECM components through activation of gelatinase A in rat corneas.

Animals↗
PubMed2000

Wound healing patterns following perforation sustained during laser in situ keratomileusis.

BACKGROUND AND PURPOSE: Corneal perforation during laser in situ keratomileusis (LASIK) may interfere with flap adhesion and wound healing. The purpose of this study was to investigate wound healing patterns following corneal perforation sustained during LASIK in rabbits. METHODS: Forty-two pigmented rabbit eyes underwent LASIK surgery with 5.0-mm excimer laser treatment under the corneal flap. Animals were divided into two groups: group I (n = 19) underwent the regular LASIK procedure with -10.0 D treatment, without perforation; in group II (n = 23), the cornea was perforated with the excimer laser. Treatment was discontinued once perforation was observed, and the corneal flap was replaced without sutures. Slit-lamp biomicroscopy, photography, and scatterometry were performed preoperatively and at 1 and 2 days, 1 week, and weekly up to 1 month, 2 months, and 3 months postoperatively. Animals were killed at 1 day, 1 week, 1 month, and 3 months postoperatively and processed for light microscopic, electron microscopic, and immunohistochemical examinations. RESULTS: In group I, the corneas remained clear throughout the experiment. In all eyes, the interface was not readily discernable clinically or histologically. Corneal wound healing was accompanied by minimal cell infiltration. Epithelial hyperplasia at the flap edge was noted at 1 week. Myofibroblast activation was found at the epithelial wedge where there was an epithelial basement membrane break. In group II, the anterior chamber was shallow with no iris incarceration at the end of surgery. The corneas were clear (n = 6) or showed mild to moderate edema (n = 12). Corneal edema peaked at 3.6 +/- 5.0 days and subsided thereafter. Corneal wounds healed similarly to those in group I except at the perforation site. The break in Descemet's membrane and endothelium was covered with a fibrin plug on day 1, which resolved thereafter. There was no statistically significant difference in the incidence of postoperative infection (p = 1.0) or flap displacement (p = 0.69) rates between the two treatment groups. The scatterometry index peaked at 2 to 3 weeks postoperatively and was significantly higher in group II than in group I (p < 0.001). CONCLUSIONS: Although corneal perforation during LASIK surgery may interfere with immediate postoperative flap adhesion, corneal wound healing following LASIK perforation may be similar to that after an uncomplicated LASIK procedure.

Actins↗
PubMed2000

Photochemical keratodesmos for repair of lamellar corneal incisions.

PURPOSE: To determine the efficacy of photochemical keratodesmos (PKD) for closing surgical incisions in the cornea of enucleated rabbit eyes compared with that achieved using sutures and self-sealing incisions. METHODS: A 3.5-mm incision, at an angle parallel to the iris, was made in the cornea of enucleated New Zealand White rabbit eyes. The intraocular pressure required to cause leakage (IOP(L)) from the untreated incision was then recorded. Photochemical keratodesmos treatment was then performed by application of a dye, Rose Bengal (RB), in saline solution to the surfaces of the incision wound, followed by laser irradiation at 514 nm from an argon ion laser. Immediately after treatment, the IOP(L) was measured. Both dose and laser irradiance dependencies were studied in five or more eyes for each condition and appropriate control eyes. The IOP(L)s were compared with those obtained using conventional interrupted 10-0 nylon sutures. Other dyes were tested in a similar fashion. RESULTS: The IOP(L) of 300 mm Hg was obtained using a fluence of 1270 J/cm(2) with an irradiance of 1.27 W/cm(2) (laser exposure time, 16 minutes 40 seconds). No sealing was observed using dye or light alone where control pressures of approximately 30 mm Hg were found. At higher dose (1524 J/cm(2)) and irradiance (3.82 W/cm(2); 6 minutes 35 seconds), PKD was less effective, which may be attributable to thermal effects. PKD produced IOP(L)s similar to those in closure by sutures. Other dyes such as riboflavin-5-phosphate and N:-hydroxy-pyridine thione also produced efficient bonding after PKD. Nonphotochemically active dyes did not produce significant increases in the IOP(L) at which leakage occurred. CONCLUSIONS: The increase in IOP(L) after PKD treatment, comparable with that with sutures, in enucleated rabbit eyes demonstrates the feasibility of this technique ex vivo.

Animals↗
PubMed1999

Double-knot transscleral suture fixation technique for displaced intraocular lenses.

PURPOSE: To describe a simplified new technique for repositioning and attaching a suture to the haptic of a displaced posterior chamber intraocular lens (IOL). METHODS: We describe a double-knot technique for repositioning and transscleral suture fixation of a subluxed posterior chamber IOL after penetrating keratoplasty. Two 10-0 Prolene transscleral sutures on straight needles are passed around the IOL haptic, tied extraocularly, and used to secure the repositioned haptic of the IOL. A second knot ties the transscleral suture in the scleral bed, stabilizing the haptic in the ciliary sulcus. RESULTS: In the case described, the IOL was stable and well positioned 2 months after surgery. CONCLUSION: The double-knot technique for intraocular repositioning and transscleral suture fixation of displaced posterior chamber IOLs reduces the extensive intraocular manipulation and scleral incisions required for IOL exchange and may reduce chronic irritation associated with iris fixation.

Animals↗
PubMed1999

Immunolocalization and gene expression of matrilysin during corneal wound healing.

PURPOSE: To investigate the protein level of matrilysin and stromelysin-1 and the gene expression of matrilysin in rat corneas after excimer keratectomy using immunofluorescence staining, reverse transcriptase-polymerase Chain Reaction (RT-PCR), and in situ hybridization. METHODS: Rat corneas were treated with 3-mm excimer laser keratectomy (193-nm ArF). Unwounded corneas served as controls. Confocal microscopy was used to immunolocalize matrilysin protein at 6 hours, 1 day, 3 days, 1 week, 4 weeks, and 8 weeks after surgery. RT-PCR was performed to analyze matrilysin mRNA in unwounded controls and in 3-day wounded corneas. In situ hybridization was performed to localize matrilysin mRNA. RESULTS: Matrilysin was immunolocalized to the epithelial layers of unwounded and wounded corneas, predominantly to the leading edge at 6 hours and 1 day after wounding and to the epithelial layer at 3 to 7 days after surgery. Stromelysin-1 was expressed in the deep stromal layer in the first 3 days after wounding and in the area of newly synthesized stromal matrix 1 week after surgery. Upregulation of matrilysin expression 3 days after wounding was confirmed by RT-PCR. In situ hybridization revealed that the gene expression of matrilysin in rat corneas was upregulated during the migration phase (6 hours, 1 day) and that matrilysin mRNA was predominantly localized to the basal cell layers during the subsequent cell proliferation phase (7 and 14 days). CONCLUSIONS: Basal epithelial cells express matrilysin during the migration proliferation phase of corneal wound healing after excimer keratectomy.

Animals↗