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Biomedical subjects

J J Rowsey

Publications and source records attributed to J J Rowsey.

At least 19 recordsLinked to original sources

Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases.

Healing of corneal alkali injuries remains a severe clinical challenge. The authors evaluated the effect of a new synthetic inhibitor of matrix metalloproteinases (GM6001 or N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl]-L-tryptophane methylamide) on preventing ulceration of rabbit corneas after alkali injury. Topical treatment of corneas with severe alkali injuries with 400 micrograms/ml or 40 micrograms/ml GM6001 alone prevented ulceration for 28 days, although 8 of 10 corneas treated with vehicle perforated. Corneas treated with 4 micrograms/ml GM6001 had midstromal depth ulcers. Corneas treated with 400 micrograms/ml of GM6001 contained very few inflammatory cells and had significantly reduced vessel ingrowth compared with vehicle-treated corneas. Epithelial regeneration after moderate alkali injuries also was investigated. Persistent epithelial defects developed 4 days after moderate alkali injury in rabbit corneas treated with vehicle and progressively increased to an average of 20% of the original 6 mm diameter wound by 27 days after moderate alkali injury. By contrast, epithelial regeneration was complete and persisted for 21 days for corneas treated with a formulation containing GM6001 (400 micrograms/ml), epidermal growth factor (10 micrograms/ml), fibronectin (500 micrograms/ml), and aprotinin (400 micrograms/ml). Sporadic punctate staining developed in 20% of the corneas treated with the combination of agents between days 21-28 after moderate alkali injury. These results demonstrate that topical application of GM6001 prevented corneal ulceration after severe alkali injury and that a combination containing GM6001, epidermal growth factor, fibronectin, and aprotinin promoted stable regeneration of corneal epithelium after moderate alkali injury.

Alkalies

Ocular infections associated with Comamonas acidovorans.

Comamonas acidovorans (Pseudomonas acidovorans) is a ubiquitous gram-negative rod. Although generally considered nonpathogenic, we found C. acidovorans to be associated with six cases of ocular infections. The organism was the only isolate in three cases, whereas an association of other organisms was present in three cases. The multiple resistance patterns of these strains to antibiotic susceptibility testing emphasizes the need for culturing ocular infections. We recommend the identification and susceptibility testing of all ocular gram-negative rod isolates.

Adolescent

Clinical use of the 193-nm excimer laser in the treatment of corneal scars.

Phototherapeutic keratectomy using a 193-nm excimer laser was performed at four centers on 33 sighted patients with corneal opacity and/or irregular astigmatism. Pathologic conditions included anterior stromal and superficial scarring from postinfectious and posttraumatic causes, including inactive herpes simplex virus, anterior corneal dystrophies, recurrent erosions, granular dystrophy, and band keratopathy. Most patients received peribulbar anesthesia and underwent removal of the epithelium prior to laser ablation. A majority of patients had a reduction in the amount of corneal scarring and approximately half had improved visual acuity. No intraocular reaction or changes in endothelial counts were seen, and some patients avoided the need for penetrating keratoplasty. Reepithelialization usually occurred within 4 or 5 days and we noted no significant scarring secondary to use of the laser. It was difficult to eliminate preexisting irregular astigmatism despite the use of surface modulators, such as methylcellulose. A hyperopic shift secondary to corneal flattening was encountered in approximately 50% of the patients. A combination of myopic ablation, followed immediately by a secondary hyperopic steepening, may minimize this refractive change. The 193-nm excimer laser is an effective new tool in the treatment of selected patients with superficial corneal opacity from a variety of conditions.

Adult

Infectious endophthalmitis following sutureless cataract surgery.

Within the last 6 months, three cases of infectious endophthalmitis following sutureless cataract surgery have been referred to us. Two of these cases followed uncomplicated sutureless phacoemulsification with intraocular lens implantation. One case was complicated by a postoperative hyphema with additional surgery for clot removal 2 days following the initial procedure.

Aged

Effect of oxygen free radicals on corneal collagen.

Corneal collagen was labeled in vivo by injection of 14C-proline into the anterior chamber of rabbit eyes. The isolated corneal collagen was incubated in iron-free phosphate buffered saline (pH 7.4) containing 1 mM ascorbate and 0.1 mM CuSO4 for either 1 hour or 3 hours at 37 degrees. Addition of 2 volumes of 8M urea-1 mM dithiothreitol and heating for 1 min at 100 degrees solubilized virutually all of the collagen in the control incubations but left a significant amount of insoluble collagen in specimens exposed to the hydroxyl radical generating system. This residue amounted to 19% and 38% of the initial radioactivity in samples incubated for 1 h and 3 h, respectively. The chromatographic profiles (gel filtration on CL-4B) of the soluble fraction showed an increase in both aggregation and degradation products of collagen in the 1 h incubation mixture, whereas after 3 h there was an increase only in degradation products. These observations suggest that additional crosslinking of the soluble collagen aggregates observed at 1 h may be responsible for their subsequent disappearance at 3 h, with concomitant increase of the insoluble fraction. Collagen degradation by .OH may play a role in corneal ulceration, whereas hydroxyl radical-mediated crosslinking is consistent with age-dependent increases in insoluble collagen.

Animals

Corneal topography as a predictor of refractive change in the prospective evaluation of radial keratotomy (PERK) study.

The first operated eyes of 435 patients undergoing radial keratotomy in the Prospective Evaluation of Radial Keratotomy (PERK) study were evaluated by photokeratography to document the preoperative and postoperative corneal shape. We determined by regression analysis and analysis of variance that the corneal shape preoperatively improved the prediction of the corneal shape 6 months postoperatively in the 3-mm-clear-zone population. The reduction of myopia in all 435 eyes ranged from 1.25 to 9.75 diopters. We studied the effect of the preoperative corneal shape on this variability in the outcome of the surgery using rings 2 and 7 on photokeratography and corneal diameter. In the 3-mm-clear-zone group, eyes with flat prolate corneas had a greater reduction in myopia (4.65 D); those with steeper, more spherical corneas had less reduction in myopia (3.48 D). In addition, eyes with a 3-mm clear zone and flat central corneas alone (8.0 mm = 42.19 D) flattened approximately 0.75 D more than those with steep central corneas (7.0 mm = 48.21 D). In the 3.5-mm and 4.0-mm clear zone groups, the change in corneal curvature was not related to the preoperative curvature. A stepwise regression analysis of the 151 eyes in the 3.0-mm-clear-zone population demonstrated the following predictive equation for radial keratotomy; change in cycloplegic refraction = -14.55 + [-2.097 x average ring-2 radius] + [3.605 x average ring-7 radius] + [0.69 x horizontal corneal diameter] + [0.079 x age] + [-0.379 x spherical equivalent cycloplegic refraction]. There was a 1.17-D observed difference in the effect of radial keratotomy between those eyes with a steep/steep corneal topography (7.2% of the 3.0-mm-clear-zone population) and the flat/flat topography (29% of the 3.0-mm-clear-zone PERK population). A knowledge of corneal topography provides an additional tool for understanding the operative variability of radial keratotomy.

Cornea

Role of active oxygen species in corneal ulceration. Effect of hydrogen peroxide generated in situ.

Cationic glucose oxidase, prepared by amidation of its free carboxylic groups, has prolonged retention in tissues, resulting in sustained release of hydrogen peroxide generated during oxidation of endogenous glucose. Increased levels of hydrogen peroxide can inhibit superoxide dismutase activity, thereby promoting reduction of transition metal ions, particularly iron and copper, by superoxide anions. Therefore, hydrogen peroxide can generate highly reactive hydroxyl radicals through a superoxide-driven Fenton reaction. Amidated glucose oxidase injected into rabbit cornea produces corneal opacification within 3-4 days and severe corneal damage by 7 days. Ultrastructural studies revealed typical tissue lesions observed in corneal melting. Heat-inactivated amidated glucose oxidase had no effect during the first 3-4 days. However, a gradual opacification occurred thereafter, resulting in some cases, in a severe opacity by 7 days. These results are consistent with an oxidative attack on corneal glycoconjugates by radicals derived from glucose oxidase-generated hydrogen peroxide during the first 3-4 days. Invading phagocytic cells are responsible for lesions observed with the inactive enzyme and for the progression of the initial lesions caused by the active enzyme. Stimulated phagocytic cells not only produce active oxygen species during the respiratory burst, but also release neutral collagenase and acid lysosomal hydrolases that contribute to and amplify the degradation of the extracellular matrix.

Animals

Immunohistologic findings and results of treatment with cyclosporine in ligneous conjunctivitis.

Using immunohistochemical techniques, we studied ligneous conjunctival lesions from two patients. A significant immune reaction was detected that was characterized by activated T lymphocytes and focal accumulation of plasma cells and B lymphocytes. Immunofluorescent studies demonstrated that IgG was a prominent component of the amorphous hyaline material seen in these lesions. After previous treatment methods had failed, both patients were treated with excisional biopsy and topical cyclosporine. Patient 1 had a dramatic response, with complete resolution of the lesions. Patient 2 had a significant improvement resulting in small, slow-growing recurrences instead of the rapid and extensive recurrences that occurred before treatment with cyclosporine.

Adult

Accuracy and reproducibility of KeraScanner analysis in PERK corneal topography. PERK Study Group.

The measurement of the corneal radius of curvature centrally and in the corneal periphery is exceedingly difficult because of variables in photography and data acquisition. We present a technique of Automated image scanning of corneal photographs which provides a more accurate and reproducible analysis of the paracentral corneal contour. We analyzed the sources of error of corneal topography measurement. CorneaScope photographs of calibration balls were generated by each Prospective Evaluation of Radial Keratotomy (PERK) Surgical Center. The 90% confidence intervals for individual ring-radial positions on the 8.00 and 10.00 mm balls were 7.91 to 8.09 mm and 9.89 to 10.11 mm respectively. Our isopter method of analysis for clinical comparison averages all eight radii of curvature for each CorneaScopef ring. This isopter technique reduces the corresponding 90% confidence intervals to 7.96 to 8.03 and 9.95 to 10.06 mm. The measurement variability of a 10 mm calibration ball decreased in the following order: calibration ball positioning, scanner personnel, photograph movement between scans, and nonrepositioned scanning. Photographs of calibration balls demonstrate +/- 4 microns of measurement resolution and patient corneal photographs may be evaluated to +/- 40 microns. This automated scanning system provides consistent data when digitizing keratographs.

Biometry

Topical application of all-trans-retinoic acid. A look at the cornea and limbus.

A 0.1% all-trans-retinoic acid in petroleum-base ointment was applied daily in eight normal rabbit eyes. Epithelial samples were collected from the cornea and limbus of six rabbits by impression cytology at 3- to 4-day intervals. Cytological changes were followed for 21 days and the eyes subsequently harvested for histochemical, scanning electron microscopic (SEM), and transmission electron microscopic (TEM) analysis of corneal and limbal structures. Two rabbits were treated with 0.1% all-trans-retinoic acid for 24 days without impression cytology until the 21st day. On the 24th day these eyes were harvested for similar studies. Impression cytology studies of the corneal epithelium demonstrated perinuclear halos and vacuolization of the cytoplasm. Additionally, vacuolization of the cytoplasm was observed by TEM, with attendant extrusion of the cytoplasmic contents and a subjective increase in surface microvilli as seen by SEM. Histochemical analysis revealed mucinlike staining of the corneal epithelium.

Administration, Topical

Nylon suture toxicity after cataract surgery.

A cluster of symptoms and signs that appear to be related to wound closure developed in 10 of 105 consecutive patients (9.5%) who underwent uncomplicated planned extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens (PC IOL) implants. These signs and symptoms included foreign body sensation, conjunctival injection and infiltrates localized to the scleral wound, and scleral excavation underlying the running 10-0 nylon suture possibly resulting from localized scleral edema. The clinical presentation ranged from 1 to 6 weeks. Conjunctival stains demonstrated eosinophils and polymorphonuclear leukocytes in some cases. Gram stains, conjunctival cultures, and results of suture toxicology studies were negative. The authors believe that these findings represent a previously unreported complication after ECCE: acute inflammation primarily localized to the conjunctiva and sclera adjacent to the cataract wound. The etiology of this postoperative complication is yet to be determined.

Cataract Extraction

Prospective evaluation of radial keratotomy. Photokeratoscope corneal topography.

Preoperative and postoperative corneascope photographs of 368 myopic patients undergoing radial keratotomy in the Prospective Evaluation of Radial Keratotomy (PERK) study were optically scanned and digitized. A high-resolution scanning system was developed in order to quantify the preoperative and postoperative corneal shape accurately. Careful analysis of the 72 data points in the nine representative rings demonstrated that corneal topography is best represented by radius of curvature from the center to the periphery. The normal myopic cornea flattens approximately +0.28 mm from the center to the periphery, demonstrating the cornea's aspheric nature. More highly myopic patients in the PERK population (-4.50 to -8.00 diopters [D]) demonstrated corneas that are 0.08 to 0.10 mm steeper than the less myopic population (-2.00 to -3.12 D). Optical zone, patient age, and gender are all correlated to changes in corneal topography after radial keratotomy. In more myopic populations, men have corneas which are flatter than those of women by 0.09 to 0.11 mm in all rings represented on corneoscopy. Highly myopic males also experience more corneal flattening after 3.0-mm optical zone radial keratotomy. Regardless of the optical zone used in radial keratotomy, the resulting corneal topography flattens in all rings. However, the ratio of millimeters of radius of curvature change to diopters of correction is consistent for each ring. The dioptric change observed after radial keratotomy corresponds closely with the millimeters of flattening at the respective rings being examined. The central rings flatten 0.166-mm radius of curvature per diopter of refractive alteration obtained. The largest degree of corneal flattening occurs centrally, 0.72 mm, in the more highly myopic patients who underwent 3-mm optical zone radial keratotomy. The use of smaller optical zones in radial keratotomy produces larger changes in the radius of curvature and, consequently, in the amount of refraction than when larger optical zones are used. When compared with younger patients, older patients with 3.0, 3.5, and 4.0 optical zone radial keratotomies experience more central and peripheral corneal flattening. This study of the corneal topography of the myopic population demonstrates that the refractive change resulting from radial keratotomy is related to alterations in corneal topography. The use of similar modifications of the corneal surface may be effective for newer refractive surgical procedures.

Adult

Acanthamoeba keratitis and infectious crystalline keratopathy.

Two cases of Acanthamoeba keratitis and infectious crystalline keratopathy, occurring simultaneously, are presented. Three and 12 months after initiating topical corticosteroid therapy in cases 1 and 2, respectively, alpha-hemolytic Streptococcus viridans was cultured from each cornea. Topical corticosteroid therapy was initiated for the treatment of an annular stromal opacity, presumably secondary to herpes simplex keratitis. Acanthamoeba was identified in culture following penetrating keratoplasty in case 1, and Acanthamoeba polyphaga, Acanthamoeba rhysodes, and Acanthamoeba castellanii were identified using indirect fluorescent antibody staining in case 2. Histopathologic examination and electron microscopy demonstrated sheets of cocci within stromal lamellae characteristic of infectious crystalline keratopathy and double-walled encysted organisms typical of Acanthamoeba. These case reports alert one to the possibility of developing bacterial keratitis, such as infectious crystalline keratopathy, following the use of topical corticosteroids for the treatment of Acanthamoeba keratitis.

Adrenal Cortex Hormones

Three-year results of the Prospective Evaluation of Radial Keratotomy (PERK) Study.

The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center clinical trial of a standardized technique of radial keratotomy in 435 patients who had simple myopia with a preoperative refractive error between -2.00 and -8.00 diopters (D). The authors report results for one eye of each patient. The surgical technique consisted of eight incisions using a diamond micrometer knife with the blade length determined by intraoperative ultrasonic pachymetry and the diameter of the central clear zone determined by the preoperative refractive error. At 3 years after surgery, 58% of eyes had refractive error within 1.00 D of emmetropia; 26% were undercorrected and 16% were overcorrected by more than 1.00 D. Uncorrected visual acuity was 20/40 or better in 76% of eyes. The operation was more effective in eyes with a preoperative refractive error between -2.00 and -4.37 D. Between 1 and 3 years after surgery, the refractive error changed by 1.00 D or more in 12% of eyes, indicating a lack of stability in some eyes. In the 435 eyes, there was a small number of complications including six eyes that lost two or three lines of best-corrected acuity, 16 that experienced vascularization of the incisions, 2 that had delayed bacterial keratitis, and 4 that had recurrent epithelial erosions.

Follow-Up Studies

An anterior limbal approach to vitrectomy for the surgical management of infectious endophthalmitis.

We present two cases illustrating a surgical approach to the diagnosis and treatment of infectious endophthalmitis following extracapsular cataract extraction with insertion of a posterior chamber lens. In both cases, a vitrectomy was initiated through a limbal approach after clearing the anterior chamber, thus allowing improved visualization of the vitreous cavity. The vitrectomy probe was then passed through a peripheral iridotomy, the peripheral posterior capsule and/or zonules, and into the anterior vitreous. The peripheral iridotomy allowed access to the vitreous cavity for an anterior vitrectomy. The entire anterior chamber and vitreous aspirate was then analyzed for culture and sensitivity. This technique minimizes the risks of pars plana vitrectomy for endophthalmitis by improving visualization and possibly decreasing the risk of retinal detachment.

Cataract Extraction