Biomedical subjects

K K Assil

Publications and source records attributed to K K Assil.

34 records · Page 2Linked to original sources

PubMed1993

Corneal iron lines associated with the intrastromal corneal ring.

Corneal epithelial iron lines commonly occur, and their shape is characteristically influenced by the underlying corneal surface topography. We studied a pattern of iron deposition, observed after implantation of the Intrastromal Corneal Ring (KeraVision, Inc., Santa Clara, California). In five of ten patients undergoing placement of the Intrastromal Corneal Ring, an arcuate pattern of epithelial iron deposition was observed eight to 12 months postoperatively. There was no significant clinical or topographic difference over time among the corneas of patients who developed an iron line vs those who did not. Of the five patients with an arcuate epithelial iron line, three underwent explantation of their Intrastromal Corneal Ring at 12 months according to the study protocol. Iron deposition either reverted to a Hudson-Stähli pattern or disappeared in each of these three patients.

Adult↗

PubMed1993

Synchrotron X-ray diffraction in atypical macular dystrophy.

This report documents the first case of X-ray diffraction techniques aiding the diagnosis of a corneal dystrophy with a clinically ambiguous presentation. Post-operatively, a high-angle synchrotron X-ray diffraction pattern was obtained from an in vitro portion of a pathological cornea. This pattern displayed two X-ray reflections which we recently demonstrated to be unique to the high-angle X-ray diffraction patterns of both type I and type II macular dystrophy corneas; on the basis of this evidence we were able to offer a post-operative diagnosis of macular corneal dystrophy. An electron microscopical evaluation of the cornea revealed stromal lacunae at all levels and an extensive layer of vacuoles, predominantly between Bowman's layer and the anterior stroma. These vacuoles were often associated with large proteoglycan filaments, as identified by Cuprolinic blue staining. Abnormally large collagen fibrils were documented, for the first time, in a macular dystrophy cornea; they existed in localised regions, frequently adjacent to the vacuoles and abnormal proteoglycans, and could well have implications for corneal transparency. We propose that the dystrophy is an atypical variant of macular corneal dystrophy which is encompassed by the heterogeneous nature of the condition.

Aged↗

PubMed1993

Evaluation of retinal toxicity and liposome encapsulation of the anti-CMV drug 2'-nor-cyclic GMP.

PURPOSE: Human cytomegalovirus (HCMV) is an important pathogen in the immunocompromised patient. CMV retinitis is a leading cause of blindness in patients with AIDS. Ganciclovir and foscarnet are currently the treatments being used for this retinitis, but they both have major toxicities when used systemically. Intravitreal therapy with ganciclovir has been used in some patients who cannot tolerate systemic treatment. The major problem with this modality is the necessity for administration of between 1 and 3 intravitreal injections per eye per week. 2'-nor-cyclic GMP is a nucleotide analog, a cyclic phosphate derivative of ganciclovir. Neutral salts of the compound are extremely water soluble, and the charged phosphate group at neutral pH make it an ideal candidate for encapsulation into a multivesicular liposome system. METHODS: The authors evaluated the retinal toxicity of the diethanolammonium salt 2'-nor-cyclic GMP by using electroretinographic, morphologic, and ophthalmoscopic techniques after intravitreal injections in rabbit eye. RESULTS: The intraocular therapeutic index for 2'-nor-cyclic GMP is 20. At the 10 micrograms dose, electroretinogram, ophthalmoscopic examination, and both light and electron microscopy revealed no abnormalities. Toxicity was evident at 50 micrograms and higher doses with ERG changes (loss of amplitude) and retinal pathology that varied from vacuolization of the retinal pigment epithelium and loss of height of the outer photoreceptor segment to loss of the entire outer retina. In addition, an in vitro drug release half-life of 1,000 hours (more than 75 times that of ganciclovir) was found for 2'-nor-cyclic GMP in liposome, which may be able to be exploited in the therapy of patients with CMV retinitis unable to tolerate toxic systemic therapy. CONCLUSION: The anti-CMV drug, 2'-nor-cyclic GMP, may be promising for intravitreal injection, particularly if encapsulated into liposomes.

Animals↗

PubMed1992

Visual outcome after penetrating keratoplasty with double continuous or combined interrupted and continuous suture wound closure.

We reviewed the consecutive records of 296 patients who underwent corneal transplantation at our institution to compare visual outcome between those who underwent double continuous suture wound closure and those who underwent a combination of interrupted and continuous suture wound closure. Of 156 patients on whom one of these closure techniques was performed, 33 patients satisfied our inclusion and exclusion criteria. Visual outcome between the two groups was compared at three, six, and 12 months. We found significant differences (P less than .05) in average corneal curvature and refractive spherical equivalents (steeper and more myopic, respectively, for double continuous suture wound closure); keratoscopic astigmatism, refractive cylindrical error; and average number of postoperative visits (greater for combined interrupted and continuous suture wound). Visual acuity without correction was significantly better at three months in the group that received double continuous sutures (P = .026). We found no marked difference in best-corrected visual acuity, frequency of graft rejection, requirement for contact lens fit, ratio of refracted vs potential visual acuity, or intraocular pressure. Patients who underwent double continuous suture closure had more rapid visual rehabilitation, had steeper corneas, and less astigmatism than patients who underwent the combined technique suture closure.

Aged↗

PubMed1992

Efficacy of tobramycin-soaked collagen shields vs tobramycin eyedrop loading dose for sustained treatment of experimental Pseudomonas aeruginosa-induced keratitis in rabbits.

We compared the efficacy of a fortified tobramycin-soaked collagen shield to the efficacy of a single loading dose (four 50-microliters drops) of fortified tobramycin eyedrops in the treatment of New Zealand White rabbits with Pseudomonas aeruginosa-induced keratitis. Eyedrop loading-dose efficacy was evaluated with and without lateral tarsorrhaphy. Six hours after a single treatment, significantly fewer Pseudomonas colonies were present in the corneas of all three drug-treated groups as compared to the number of colonies in the corneas of balanced salt solution-treated control rabbits (P less than .006). Although no significant difference was observed between any of the drug-treated groups, lateral tarsorrhaphy was associated with a greater than tenfold decrease in the number of colony-forming units (P = .073). We found no significant difference in efficacy between a collagen shield presoaked in tobramycin, and a single loading dose of tobramycin eyedrops, in the treatment of rabbits with P. aeruginosa-induced keratitis.

Administration, Topical↗

PubMed1992

Fibrin-enmeshed tobramycin liposomes: single application topical therapy of Pseudomonas keratitis.

Treatment of bacterial keratitis requires frequent application of topical antibiotics. We studied the efficacy of a single topical administration of tobramycin incorporated in large multivesicular liposomes and enmeshed in a fibrin sealant on rabbit corneas infected with Pseudomonas aeruginosa. One cornea each of 25 New Zealand albino rabbits was infected with P. aeruginosa. Twenty-four hours later, the animals were randomly divided into five groups of five. Group A received single hourly drops (50 microliters) of fortified tobramycin (14.5 mg/ml, total of 17.4 mg). Group B received a single topical application of 3.5 mg tobramycin, in 0.1 ml multivesicular liposomes, enmeshed in a fibrin sealant with an overlaying bandage contact lens. Group C was treated in the same manner as group B without the addition of fibrin sealant. Groups D and E served as nondrug-treated controls, with group D receiving topical fibrin-enmeshed liposomes devoid of tobramycin and group E receiving hourly topical balanced salt solution (BSS) drops. All animals were killed 24 h after initiation of therapy. Significantly fewer colonies of Pseudomonas were present in corneas of all three treated groups, as compared with the two nondrug-treated control groups (p less than 0.02). There were significantly fewer colonies of Pseudomonas in groups A and B as compared with group C (p less than 0.02). No significant difference was noted between a single administration of topical fibrinen-meshed tobramycin-encapsulated liposomes (group B) and 24 doses of hourly fortified topical tobramycin (group A, p greater than 0.05). Tobramycin-encapsulated megaliposomes may serve as a useful adjunct in treatment of Pseudomonas keratitis.

Administration, Topical↗

PubMed1991

Tobramycin liposomes. Single subconjunctival therapy of pseudomonal keratitis.

The authors compared 24 doses of hourly topical fortified tobramycin (Group A) therapy with a single subconjunctival administration of multivesicular megaliposome-encapsulated tobramycin (Group B) and free subconjunctival tobramycin (Group C) in treating a rabbit model of keratitis caused by Pseudomonas aeruginosa. One cornea each of 50 rabbits was infected with P. aeruginosa for 24 hr. The animals then were divided randomly into five groups of ten each. Groups A, B, and C were treated as described. Group D received liposomes without tobramycin and Group E, hourly balanced salt solution. Significantly fewer Pseudomonas colonies were present in the corneas of all three drug-treated groups (A, B, and C) compared with the two control groups (D and E) at 24 hr (P less than 0.005). Significantly fewer Pseudomonas colonies were present in Groups A and B compared with Group C (P less than 0.02). No significant difference was noted between Groups A and B (P = 0.30). Tobramycin encapsulated in megaliposomes may be useful in treatment of pseudomonal keratitis.

Administration, Topical↗

PubMed1991

Liposome suppression of proliferative vitreoretinopathy. Rabbit model using antimetabolite encapsulated liposomes.

The effects of the antimetabolites, cytarabine (Ara-C) and 5-fluorouridine 5'-monophosphate (FUMP), encapsulated in multivesicular liposomes on formation of vitreous fibroproliferative membranes in New Zealand white (NZW) rabbits were studied. In pharmacokinetic studies, the drug half-life in the vitreous cavity was 124 hr after intravitreal administration of 1.0 mg of FUMP in liposomes. By contrast, the drug half-life after a single injection in nonliposome-treated controls was only 4.5 hr. In a heterologous dermal fibroblast model of proliferative vitreoretinopathy (PVR), there was a 92% decrease in frequency of tractional retinal detachments in rabbits receiving a single intravitreal injection of liposome-encapsulated 0.1 mg of FUMP compared with controls receiving liposomes without drug. A dose of 1 mg of Ara-C in liposome-treated rabbits was associated with only a 46% reduction in tractional detachment compared with controls. Multivesicular liposome-encapsulated FUMP may be useful for inhibiting formation of fibroproliferative membranes in the vitreous after vitreoretinal surgery.

Animals↗

PubMed1988

Sustained release of the antimetabolite 5-fluorouridine-5'-monophosphate by multivesicular liposomes.

We have developed a novel liposome for sustained drug delivery to the eye of the antimetabolite 5-fluorouridine-5'-monophosphate (FUMP), a potent metabolite of 5-fluorouracil. The in vitro half-life of FUMP incorporated within these liposomes was 585 hours. Following subconjunctival administration of 1 mg of FUMP to 13 New Zealand white rabbits, the tissue drug level at the injection site was significantly greater in the group treated with liposomes than it was in the group not treated with liposomes (p = .02). These liposomes offer the potential for sustained release of FUMP in the eye. By controlling the rate of drug release, it may be possible to reduce the need for frequent drug administration and its associated ocular toxicity as well as to improve treatment efficacy.

Animals↗

PubMed1987

Multivesicular liposomes. Sustained release of the antimetabolite cytarabine in the eye.

We entrapped the antimetabolite cytarabine hydrochloride in a multivesicular liposome for sustained drug delivery to the eye. The in vitro half-life of cytarabine release from these liposomes was 359 hours. Following subconjunctival administration of 6 mg of cytarabine to 12 rabbits, the tissue half-life of drug at the injection site was 52.5 hours in the six rabbits treated with liposomes compared with 0.2 hours in the six nonliposome controls treated with the same amount of drug in normal saline solution. The aqueous humor drug concentration peaked after 1.5 hours in both the experimental (0.4 mg/L) and control (19 mg/L) groups. In control eyes, the cytarabine level of both the tissue and aqueous humor had decreased to less than 1% of peak value by eight hours. In the liposome-treated eyes, almost 30% of the cytarabine remained in the conjunctiva and episcleral tissue after 72 hours. The difference in cytarabine levels in tissue between the liposome-treated group and controls was highly significant. By controlling the rate of drug release, it may be possible to reduce the ocular toxicity and increase the efficacy of this drug for treating ocular proliferative disorders.

Animals↗

PubMedDate not supplied

Wound healing in response to keratorefractive surgery.

Over one million Americans have undergone refractive keratoplasty since the introduction of radial keratotomy into the United States in 1978. There are now a number of alternative techniques available for reshaping the corneal surface to alter ocular refractive errors. Numerous technologic advances in the past decade now enable us to perform these procedures in a safer and more reliable fashion. The ability to control precisely the refractive outcome, however, continues to elude us and appears to be limited, in part, by interindividual variability in the wound healing response. Presently, we review the corneal wound healing response to various keratorefractive approaches and suggest some interventional strategies which might enable us to modulate more precisely our refractive results.

Animals↗

PubMedDate not supplied

Comparison of the standard combined (bidirectional) radial keratotomy technique with the undercut technique in human donor eyes.

BACKGROUND: We evaluated the efficacy of a new radial keratotomy technique, using a diamond designed to undermine the central clear zone without incising superficial stroma. METHODS: An 8-incision radial keratotomy at a 3-mm central clear zone was performed on nine pairs of human donor globes. One eye of each pair was incised using the standard combined (bidirectional) technique diamond and the contralateral eye, using the undercut bidirectional technique diamond. Paired t-tests were used to compare changes in central corneal curvature between these two groups. Microscopic analysis of incision morphology was performed on four eyes. RESULTS: Corneal topography at the 1-, 3-, and 5-mm annular zones revealed corneal flattening of 7.70 +/- 1.50 diopters (D), 6.70 +/- 1.30 D, and 5.10 +/- 1.00 D, respectively, in the undercut bidirectional technique group versus 6.20 +/- 1.70 D, 5.30 +/- 1.50 D, and 4.00 +/- 1.20 D, respectively, in the standard bidirectional technique group (P < 0.01 for each annular zone). Light microscopy (serial sections) revealed an average incision depth of 80.9 +/- 3.9% in the undercut bidirectional technique group versus 72.7 +/- 4.5% in the combined group (P < 0.01). The undercut bidirectional technique incisions undermined the central clear zone for a distance of approximately 350 microns compared to about 140 microns for the standard bidirectional incisions. CONCLUSIONS: In the human cadaver eye, the undercut technique of radial keratotomy provided greater flattening than the standard bidirectional technique. The greater amount of flattening may result from greater central extension of the undercut incisions beneath the central clear zone, from greater incision depth, or from a combination of both factors.

Aged↗

PubMedDate not supplied

Ultrastructure of picosecond laser intrastromal photodisruption.

PURPOSE: To investigate the ultrastructure of the corneal stroma after picosecond intrastromal photodisruption with a neodymium-doped yttrium-lithium-fluoride (Nd:YLF) laser. METHODS: We performed picosecond intrastromal photodisruption on six human eye-bank eyes using a lamellar technique. Thirty picosecond pulses at 1000 Hz and 20 to 25 mJ per pulse were placed in an expanding spiral pattern, the pulses separated by 15 microns. Three layers were placed in the anterior stroma, separated from each other by 15 microns. In addition, intrastromal radial and arcuate incisions were generated in two living rabbit eyes in a plane perpendicular to the corneal surface. After the procedure, the corneas were processed for scanning and transmission electron microscopy. RESULTS: Scanning electron microscopy of the eye-bank eyes demonstrated multiple, coalescing intrastromal cavities forming a layer oriented parallel to the corneal surface. These cavities had smooth inner walls. Transmission electron microscopy demonstrated tissue loss surrounding some cavities, with the terminated ends of collagen fibrils clearly evident. Other cavities were formed by separation of lamellae, with little evidence of tissue loss. A pseudomembrane was present along the margin of some cavities. Although there was occasional underlying tissue disruption along the border of a cavity, there was no evidence of thermal damage or tissue necrosis. The perpendicular photodisruptions demonstrated intrastromal cleavage of corneal collagen similar to diamond-knife incisions, with the exception of intact overlying Bowman's and epithelial layers. CONCLUSION: Intrastromal photodisruption with a Nd:YLF picosecond laser induced no thermal necrosis or coagulative change in the region of tissue interaction. Lamellar intrastromal photodisruption demonstrated both tissue loss and lamellar separation when performed with the current treatment parameters, possibly limiting ablation efficiency and predictability.

Animals↗

PubMedDate not supplied

Retrephination keratoplasty for high astigmatism after penetrating keratoplasty.

PURPOSE: We report preliminary results of a new procedure for correcting high astigmatism after penetrating keratoplasty. METHODS: The procedure entails full-thickness trephination along the original donor-recipient junction with careful suturing in a combined interrupted and running fashion. Four eyes of four patients with severe astigmatism and myopia after penetrating keratoplasty underwent the procedure. RESULTS: High preoperative cylinder ranging from 4.50 to 16.00 D (mean 9.00 D) was reduced to 0.50 to 3.50 D (mean 1.90 D) at the last examination (between 3 to 6 months). Spherical equivalent myopia ranging from -2.00 to -10.25 D (mean -4.90 D) was essentially unchanged at plano to -9.00 D (-4.70 D) at the last examination. Overall, there was a mean refractive cylinder reduction of 7.10 D (79%). CONCLUSION: Retrephination after penetrating keratoplasty appears to be an acceptable alternative for correcting high astigmatism, and had only a small effect on the level of myopia.

Astigmatism↗

PubMedDate not supplied

Electron microscopic evaluation of intrastromal corneal rings explanted from nonfunctional human eyes.

BACKGROUND: Intrastromal corneal rings (ICRs) often exhibit small deposits in association with their suture holes. We assessed the morphology of four such deposits. METHODS: Four ICRs, explanted from nonfunctional human eyes, were examined by scanning electron microscopy and transmission electron microscopy. RESULTS: The surface of the suture hole deposits consisted of a disorganized convolution of collagenous lamellae. Within individual lamellae, however, the collagen fibrils tended to orientate parallel with one another. The deposits consisted of an amorphous material interspersed with curved cellular processes, collagen fibrils of variable diameter, and proteoglycan macromolecules. CONCLUSIONS: We propose that the mechanism which regulates stromal remodeling is amended in the region of the ICR suture holes. Due to their location, suture hole deposits have no optical significance; however, evaluation of their morphology provides insights into the wound-healing properties of the corneal stroma following ICR insertion.

Blindness↗

PubMedDate not supplied

Comparison of astigmatic axis in the seated and supine positions.

BACKGROUND: Refractive error is assessed in the seated position while keratorefractive procedures are performed in the supine position. Since position-induced ocular torsion could yield suboptimal results from improper axis alignment, this study was undertaken to ascertain whether ocular cyclotorsion occurs when a subject moves from a seated to supine position. METHODS: Fifty eyes of 29 subjects with refractive cylinder greater than 0.50 diopters were enrolled. Refraction was done with a phoropter and the correction was placed in a trial frame using plus cylinder. Astigmatic axis was determined in the seated and supine positions for 32 eyes by utilizing the "rocking the cylinder" technique and for 32 eyes using the Jackson cross cylinder. Both techniques were used for 14 eyes. RESULTS: No statistically-significant difference for cylinder axis measured in the seated versus supine position was observed using the rocking the cylinder (4.3 degrees standard deviation [SD], 3.5 degrees, range 0 degrees to 13 degrees, p = NS) or the Jackson cross cylinder methods (2.3 degrees, SD, 1.9 degrees, range 0 degrees to 7 degrees, p = NS). Approximately 25% of eyes had a change in axis of 7 degrees to 16 degrees. CONCLUSIONS: These data suggest that the cylinder axis does not change significantly or predictably when most subjects move from the seated to supine position. The Jackson cross cylinder method seems more accurate and reproducible than the rocking the cylinder technique in determination of astigmatic axis under these circumstances.

Adult↗