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Biomedical subjects

Walter J Stark

Publications and source records attributed to Walter J Stark.

At least 19 recordsLinked to original sources

Modified microkeratome-assisted posterior lamellar keratoplasty using a tissue adhesive.

OBJECTIVE: To compare graft stability and astigmatic change using suture vs tissue adhesive in an experimental model of microkeratome-assisted posterior lamellar keratoplasty. METHODS: A 300-microm-thick partial flap keratectomy was performed in human donor corneoscleral rims using an artificial anterior chamber and a manual microkeratome. The flap stopped at the left central opening border, providing a wide hinge to add stability. After flap reflection, a 6.25-mm trephination was performed to obtain a disc of posterior stroma, Descemet membrane, and endothelium. The disc was positioned in a sutureless fashion, and the flap secured with either 5 interrupted sutures or a chondroitin-sulfate-aldehyde-based adhesive. Increasing intrachamber pressures were created to detect graft stability. Videokeratographic data were recorded to evaluate astigmatic change. RESULTS: The mean (SD) astigmatic change was 3.08 (0.84) diopters (D) in the sutured group and 1.13 (0.55) D in the glued group (P = .008). Mean (SD) resisted pressures were 95.68 (27.38) mm Hg and 82.45 (18.40) mm Hg in the sutured and glued groups, respectively (P = .97). CONCLUSION: This modified technique of microkeratome-assisted posterior lamellar keratoplasty showed excellent graft stability in both groups. Flaps sealed with the novel tissue adhesive had reduced astigmatic changes in our experimental model. CLINICAL RELEVANCE: Sutureless microkeratome-assisted posterior lamellar keratoplasty using tissue adhesive may become a new alternative in the surgical treatment of corneal endothelial disorders.

Aged↗

Urate deposition in the iris and anterior chamber.

OBJECTIVE: To report on a patient with clear gelatinoid deposits on the iris and in the anterior chamber (AC). DESIGN: Observational case report. METHODS: Examination of AC aspirate and iris and conjunctival biopsies by light and transmission electron microscopy. MAIN OUTCOME MEASURES: Clinical and histopathological findings. RESULTS: Analysis of the aqueous humor and iris ultrastructure disclosed the presence of urate deposits. CONCLUSIONS: Urate deposition in the iris and anterior chamber rarely occurs.

Aged↗

Clinical profile and early surgical complications in the Cornea Donor Study.

PURPOSE: The Cornea Donor Study was designed to investigate the safety and efficacy of older donor corneal tissue compared with younger donor tissue in recipient eyes at moderate risk to the graft from progressive endothelial failure. Baseline patient data, including indications for transplant, intraoperative complication rates, and early postoperative complication rates are described herein. METHODS: This study was a multicenter prospective, double-masked, controlled clinical trial. RESULTS: Fuchs dystrophy was the most common indication for corneal transplantation (61%). Intraoperative complications occurred in 33 (3%) patients. A persistent epithelial defect was the most commonly reported postoperative complication, occurring in 92 patients (8%). CONCLUSION: Intraoperative and postoperative complication rates were low. There was no apparent association between donor or recipient age and either intraoperative or early postoperative complication rates.

Adult↗

Analysis and documentation of progression of Fuchs corneal dystrophy with retroillumination photography.

PURPOSE: Fuchs corneal dystrophy (FCD) is a degenerative disorder of the cornea that is characterized by the progressive accumulation of guttae, which are small excrescences of Descemet's membrane. We describe a method for documenting the location and number of guttae, and ask whether disease progression can be observed during relatively short periods. METHODS: Patients with FCD were imaged by standard retroillumination photography with a slit lamp. Scanned photographs were analyzed by using NIH ImageJ software to determine the number of individual guttae and areas of confluence. RESULTS: In 4 FCD patients, photographs taken 23 to 30 months apart revealed that, once formed, individual guttae and their relative positions persisted during this period. Very few guttae disappeared, and the emergence of many new guttae was observed. Determination of the area with confluent guttae was used to quantify disease stage. CONCLUSIONS: Computer-assisted analysis of retroillumination photographs is proposed as an effective way to document the number and distribution of individual guttae. Although the disease typically progresses slowly during decades, we have been able to detect the formation of new guttae within only 2 years. This rapid assessment of disease progression could be used to measure phenotypic differences between genetic subtypes of FCD. It also could provide important baseline information and methodology for clinical trials of therapeutic options, should these become available.

Diagnostic Techniques, Ophthalmological↗

Linkage of late-onset Fuchs corneal dystrophy to a novel locus at 13pTel-13q12.13.

PURPOSE: To identify the gene locus underlying the inheritance of late-onset Fuchs corneal dystrophy (FCD) in a large white kindred. METHODS: Genotypes of small tandem repeat polymorphisms were obtained from 17 affected and 3 unaffected family members, followed by genetic linkage analysis. RESULTS: In this family, classic late-onset FCD appeared to be inherited as a single, dominant Mendelian trait. In two exceptional sibships, however, children aged 10 and 13 years had FCD. In each sibship, both parents were found to be affected, opening the possibility that this unusually early age of onset was the result of homozygosity for an FCD mutation. Genotype results, however, were not consistent with consanguinity of the parents, who appear to have independent cases of FCD. A whole-genome linkage scan mapped FCD to a single locus at 13pTel-13q12.13, with significant two-point LOD scores of 3.91 at D13S1236 and 3.80 at D13S1304. The 26.4-Mb disease interval contains the chromosome 13 nucleolus organizer (RNR1), the centromere, and 44 annotated protein-encoding genes. So far, exons of 10 of these genes have been screened, but no mutations have been found. CONCLUSIONS: FCD1 is the first genetic locus to be identified for late-onset FCD, a common disease of the aging cornea. The exceptional early onset of the disease observed in two children is unusual and might be the result of digenic interaction between FCD1 and an independent late-onset FCD mutation.

Adolescent↗

Identical excimer laser PTK treatments in rabbits result in two distinct haze responses.

PURPOSE: To obtain objective light-scattering measurements to test a hypothesis that identical PTK treatments cause distinct low- and high-level light-scattering responses in rabbit corneas. METHODS: An excimer laser was used to produce identical 6-mm diameter phototherapeutic keratectomy treatments (PTK) in 32 pigmented rabbits. Eyes were treated by performing a 40-microm epithelial ablation, followed by a 100-mum stromal PTK. Objective scattering measurements were made before treatment, weekly up to 5 weeks, and then biweekly to 9 weeks. Confocal microscopy was performed on several corneas at 4 and 7 weeks. RESULTS: Mean scattering levels split into distinct low- and high-scattering groups 2 weeks after treatment and remained distinct until week 7 (P < 0.003). Scattering in the low group reached a broad peak that lasted from weeks 2 to 4 at approximately 3 times the pretreatment level. Scattering in the high group peaked at 3 weeks at approximately 12 times the pretreatment level. Scattering levels diminished after reaching their peaks. Confocal images showed a band of highly reflective material in the anterior stroma that extended much deeper in corneas from the high group. The reflective band in the highly scattering corneas obscured the posterior stroma from view for up to 5 weeks. CONCLUSIONS: Quantitative scattering data obtained with the scatterometer suggest that identical PTK treatments indeed result in distinct low- and high-level light-scattering responses in rabbits.

Animals↗

A common locus for late-onset Fuchs corneal dystrophy maps to 18q21.2-q21.32.

PURPOSE: To identify the genetic basis of late-onset Fuchs corneal dystrophy (FCD). METHODS: Phenotypes and genotypes at 1107 short tandem repeat polymorphism markers were obtained for 43 affected and 33 unaffected individuals in three large families. Two-point genetic linkage analysis was performed with MLINK and multipoint linkage with SimWalk 2.89. RESULTS: In each family, the most significant cluster of two-point lod scores mapped to chromosome 18, at 18q21.2-q21.3. The highest two-point lod score for each family was at D18S1129, with scores of 3.41, 2.89, and 2.45, with a combined two-point lod score of 7.70. Multipoint analysis yielded a maximum score of 5.94 at D18S1129 for a dominant Mendelian trait exhibiting 85% penetrance and 15% phenocopy rate. Disease interval haplotypes for each family are different. CONCLUSIONS: FCD2, at 18q21, is the second genetic locus identified for late-onset FCD. Presence of this same locus in all three families may indicate its widespread involvement in late-onset FCD. Allelic differences between disease-associated haplotypes in the families leave open the possibility of independent mutations in the same gene. The incomplete penetrance and high phenocopy rate observed at FCD2 suggest that the origin of FCD in these three families is complex and also depends on other genetic loci or environmental factors.

Adult↗

Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients.

PURPOSE: To measure the achievable perioperative aqueous concentration of the commercially available topically administered fourth generation fluoroquinolones, moxifloxacin 0.5% ophthalmic solution, and gatifloxacin 0.3% ophthalmic solution, and to correlate this concentration with the agents' biological efficacy in the aqueous humor of patients undergoing routine cataract surgery. DESIGN: Prospective, randomized, parallel, double-masked, clinical trial. PARTICIPANTS: Fifty patients undergoing cataract extraction. METHODS: Patients (n = 25) were given perioperative topical moxifloxacin 0.5% or topical gatifloxacin 0.3% (n = 25). One drop of antibiotic was administered every 10 minutes for 4 doses beginning 1 hour prior to surgery. Aqueous humor was sampled via paracentesis and antibiotic concentrations were determined using validated high performance liquid chromatography (HPLC) procedures. Dilution analyses were performed to determine the biological efficacy of the agents in the aqueous against Staphylococcus epidermidis, the most common cause of postcataract endophthalmitis. MAIN OUTCOME MEASURES: Aqueous humor antibiotic concentrations were measured using HPLC and microdilution bioassay techniques. Biological activity was measured as minimal inhibitory dilution and minimal bactericidal dilution. RESULTS: Aqueous humor concentrations for moxifloxacin via HPLC analysis were 1.80 (+/-1.21) microg/ml, whereas those for gatifloxacin were 0.48 (+/-0.34) microg/ml. This 3.8-fold difference in aqueous humor antibiotic concentrations was statistically significant (P = 0.00003). Similarly, the biological dilution analysis of the aqueous humor samples showed that moxifloxacin attained an estimated activity of 2.1 microg/ml, whereas the gatifloxacin activity was approximately 0.4 mug/ml, which represented a 4.9-fold difference. CONCLUSIONS: This study demonstrated that after topically administered perioperative antibiotics with cataract surgery, moxifloxacin 0.5% ophthalmic solution achieved a statistically significantly higher concentration in aqueous humor compared with gatifloxacin (P = 0.00003). Results from the broth dilution analysis showed that moxifloxacin 0.5% was biologically more active against S. epidermidis than gatifloxacin 0.3% in aqueous humor after topical application. There were no adverse events reported, and incision wounds healed quickly and as expected.

Administration, Topical↗

Inflow of ocular surface fluid into the anterior chamber after phacoemulsification through sutureless corneal cataract wounds.

PURPOSE: To report inflow of extraocular fluid after phacoemulsification with use of sutureless corneal incisions. DESIGN: Interventional case series. METHODS: setting: Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland. patients: Eight patients (three women), aged 58 to 91 years, showing minimal bleeding from the limbal capillary bed during phacoemulsification. intervention: Surgery was performed through a 2.8-mm limbal incision. External pressure simulating patient manipulation was applied before and after wound hydrosealing with an irrigation cannula. main outcome measures: Inflow of blood-tinged tear fluid into the anterior chamber through the wound was monitored by using digital video. RESULTS: Inflow of extraocular fluid was observed in all eyes when the cannula was released, even after wound hydrosealing. Two patients showed spontaneous fluid inflow. CONCLUSIONS: Tested sutureless corneal incisions allow inflow of extraocular fluid into the anterior chamber after phacoemulsification. This may permit intraocular contamination leading to endophthalmitis.

Aged↗

Cataract surgery in patients with Fuchs' corneal dystrophy: expanding recommendations for cataract surgery without simultaneous keratoplasty.

OBJECTIVE: To evaluate the use of preoperative pachymetry in patients with Fuchs' dystrophy who are undergoing cataract extraction to predict the need for future penetrating keratoplasty and to compare these findings with current published recommendations. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: A series of patients with Fuchs' dystrophy (136 eyes) undergoing cataract surgery. METHODS: We reviewed the medical records of 136 patients with Fuchs' dystrophy who underwent phacoemulsification and intraocular lens implantation between October 1990 and May 2002. MAIN OUTCOME MEASURES: Preoperative and postoperative visual acuity, pachymetry, and postoperative corneal decompensation requiring penetrating keratoplasty. RESULTS: The average preoperative corneal thickness was 584+/-39.5 microm (range, 482-674 microm). Fifty eyes (36.8%) had preoperative corneal thickness of > or =600 microm. The average postoperative best-corrected visual acuity (BCVA) was 20/33 (range, 20/15-20/250). Of the 50 eyes with preoperative pachymetry measurements of > or =600 microm, 5 (10%) progressed to penetrating keratoplasty; 90% of the 50 eyes did not need corneal transplants within the first year after cataract surgery and had an average postoperative BCVA of 20/35 (range, 20/20-20/200). Of those with a corneal thickness of > or =640 microm, 83% did not need a corneal transplant within this same time period and had an average postoperative BCVA of 20/50 (range, 20/20-20/200). CONCLUSIONS: To avoid unnecessary cost and delay in visual rehabilitation, we suggest changing the current recommendations for an initial triple procedure for eyes with preoperative pachymetry measurements of >600 microm. Our data suggest that current cataract removal techniques allow for excellent visual rehabilitation in patients with Fuchs' dystrophy who have a preoperative corneal thickness of >600 microm, and we suggest that preoperative pachymetry measurements of >640 microm may be a better guideline. This recommendation can be further expanded above 640 mum if a visual acuity of less than 20/20 is acceptable. A prospective randomized controlled study is required for validation of this analysis.

Adult↗

A morphologic study of Fuchs dystrophy and bullous keratopathy.

PURPOSE: To describe the morphologic features of Fuchs corneal dystrophy and compare them with those of bullous keratopathy. METHODS: This was an observational case series. The study group consisted of 32 corneal buttons with a diagnosis of Fuchs dystrophy and the comparison group consisted of 22 corneal buttons with bullous keratopathy. Morphologic analysis was performed of corneal buttons from patients with the clinical diagnosis of Fuchs dystrophy or bullous keratopathy by light and electron microscopy. RESULTS: The main outcome measure was identification of degenerated keratocytes, granular material in and around keratocytes, and lipid keratopathy. The overall morphologic features of Fuchs dystrophy and bullous keratopathy are similar to those described in previous literature. A high proportion of keratocytes exhibited degenerative changes (78.9% in Fuchs dystrophy versus 50.5% in bullous keratopathy). Granular material was identified in and around variably degenerated keratocytes in all cases of Fuchs dystrophy and in 14 of 22 (64%) of the corneas with bullous keratopathy. The percentage of keratocytes with granular deposits was higher in Fuchs dystrophy corneas as compared with corneas with bullous keratopathy (51.7% versus 14.1%, P < 0.0005). Lipid keratopathy was a common occurrence in both Fuchs dystrophy and bullous keratopathy (23/32 [72%] versus 12/22 [55%]). CONCLUSIONS: Histopathologic changes in the corneal stroma and keratocytes occur in Fuchs dystrophy. Secondary lipid keratopathy ensues and may contribute to corneal haze. A higher proportion of keratocytes in Fuchs dystrophy have granular deposit than in bullous keratopathy. That a high proportion of keratocytes had degenerative changes in both Fuchs dystrophy and bullous keratopathy suggests that keratocytes may degenerate secondary to altered stromal microenvironment because of endothelial cell loss.

Aged↗

Subluxation of iris-sutured intraocular lenses and results of a closed chamber technique for repositioning after penetrating keratoplasty.

PURPOSE: To describe subluxation of iris-fixated intraocular lenses (IOLs) after penetrating keratoplasty (PK) as a postoperative complication and report the long-term outcomes of a closed-chamber refixation technique used in the management. METHODS: This was a retrospective, noncomparative interventional case series in which 19 consecutive patient charts with a subluxated iris-fixated IOL after PK were retrospectively reviewed. Fourteen of the patients underwent surgery using a closed-chamber refixation technique. These patients were evaluated for visual outcome and surgical complications associated with the procedure. RESULTS: In 13 patients, postoperative follow-up was available. In all 13 cases, the fixated IOL appeared stable and remained well positioned during a follow-up period of 56 months (range, 6-122). All patients (100%) achieved improved uncorrected visual acuity. The postoperative visual acuity ranged from 20/20 to 20/100 with a mean of 20/40. Vitreous hemorrhage occurred in 1 patient, and an additional patient required a second surgery using the same technique. Both of these patients did well with a final visual acuity of 20/40 and 20/50, respectively. CONCLUSIONS: Subluxation of iris-fixated IOL after PK can occur as a postoperative complication. The technique that we herein describe enables secure refixation of subluxated IOLs and yields favorable long-term results.

Adult↗

Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of fuchs corneal dystrophy.

PURPOSE: To characterize the genetic basis and phenotype of inherited Fuchs corneal dystrophy (FCD). METHODS: DNA from blood was used for genome-wide linkage scans with tandem repeat polymorphisms. Mutation detection involved sequencing PCR-amplified exons. Families with FCD were clinically evaluated and graded on the Krachmer severity scale. Confocal specular microscopy visualized the morphology of endothelial guttae, small protrusions of Descemet's membrane that are characteristic of FCD. RESULTS: Linkage was obtained to 1p34.3-p32 for the autosomal dominant kindred originally reported by Magovern in 1979. All 21 cases with FCD and one with posterior polymorphous dystrophy were heterozygous for L450W, a novel point mutation in the COL8A2 gene. Of 62 independent cases of familial FCD, none had the previously reported mutations in COL8A2. Corneal guttae in COL8A2 patients were small, rounded, and associated with the endothelial cell center. This contrasts with common FCD, in which guttae were larger, sharply peaked, and initially positioned at edges of endothelial cells. The profile of age and disease severity for the L450W FCD kindred suggested that disease onset occurred in infancy, compared with an average age of onset of 50 years estimated for 201 familial FCD patients in 62 other families. CONCLUSIONS: A novel pathogenic L450W COL8A2 mutation was identified and its highly distinctive pathology characterized. This indicates that COL8A2 mutations give rise to a rare subtype of FCD. This study also provides the first direct evidence that COL8A2-FCD progresses from early to late stages in 25 years, a rate similar to that estimated for late-onset FCD.

Adolescent↗

Fuchs corneal dystrophy: aberrant collagen distribution in an L450W mutant of the COL8A2 gene.

PURPOSE: To characterize histologically Descemet's membrane in an early-onset Fuchs corneal dystrophy (FCD) COL8A2 mutant and compare these findings with corneas from late-onset FCD and normal corneas. METHODS: A corneal explant from a patient with the L450W COL8A2 mutation and others with late-onset disease were studied with antibodies to collagens IV, VIIIA1, VIIIA2, fibronectin, and laminin. Transmission electron microscopy was performed on a portion of the explant. Control explants included eye bank corneas without known disease and surgical explants from unrelated conditions. RESULTS: In normal corneas, a regular array of colocalized COL8A1 and COL8A2 was observed in the anterior half of Descemet's membrane. In the L450W mutant, Descemet's membrane was several times thicker than normal and traversed by refractile strands and blebs that stained intensely for COL8A2, a feature also observed in late-onset FCD. Both the alpha1 and alpha2 subtypes of collagen VIII were observed at high levels along the anterior edge of Descemet's, another abnormal feature also found in late-onset FCD. Ultrastructure of the L450W cornea revealed a well-formed anterior banded layer more than three times thicker than normal. An unusual, thin internal layer was rich in patches of wide-spaced collagen. The layer is a distinctive pathologic structure that is associated with FCD and is characterized by approximately 120 nm periodicity and the presence of collagen VIII. Depositions of collagen IV, fibronectin, and laminin were also greatly increased in the of posterior Descemet's membrane, yet another general feature shared between early- and late-onset disease. CONCLUSIONS: Early-onset COL8A2 L450W disease involves massive accumulation and abnormal assembly of collagen VIII within Descemet's membrane, a process that is presumed to begin during fetal development. Both early- and late-onset subtypes of FCD appear to be the result of abnormal basement membrane assembly rather than a primary defect in endothelial metabolism.

Collagen Type IV↗

Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery.

A prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10 min for four doses beginning 1 h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (p < 0.01) than those for gatifloxacin.

Administration, Topical↗

Astigmatism outcomes of horizontal temporal versus nasal clear corneal incision cataract surgery.

PURPOSE: To compare the short- and long-term astigmatism outcomes after cataract surgery using temporal clear horizontal corneal incisions and nasal horizontal clear corneal incisions. SETTING: Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA. METHODS: This retrospective study included a consecutive series of eyes having phacoemulsification with implantation of a 6.0 mm foldable acrylic intraocular lens through a 3.5 mm horizontal clear corneal incision at 180 degrees (temporal incision in right eyes, nasal incision in left eyes). Astigmatism was measured by keratometry readings before surgery and 6 weeks and 12 months postoperatively. RESULTS: The mean preoperative astigmatism in the 178 eyes (94 right, 84 left) of 161 patients was 0.78 diopter (D); 54.5% of eyes had against-the-rule (ATR) astigmatism, 22.5% had with-the-rule (WTR) astigmatism, and 14.0% were astigmatically neutral. A significant shift toward WTR astigmatism occurred postoperatively. At 6 weeks, 48.3% of eyes had WTR astigmatism and 23.0% had ATR astigmatism. At 12 months, 43.8% had WTR astigmatism and 25.8% had ATR astigmatism. Vector analysis revealed a mean surgically induced astigmatism (SIA) of 1.17 D at 6 weeks and 1.04 D at 12 months. The side of the incision significantly affected SIA. At 6 weeks, temporal incisions yielded a mean SIA of 0.74 D and the nasal incisions, of 1.65 D. This trend in SIA persisted at 12 months: 0.71 D for temporal incisions and 1.41 D for nasal incisions. CONCLUSIONS: Cataract surgery using a horizontal clear corneal incision induced WTR astigmatism 6 weeks and 12 months postoperatively. Temporal incisions induced significantly less astigmatism than nasal incisions.

Aged↗