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Biomedical subjects

W D Mathers

Publications and source records attributed to W D Mathers.

At least 37 records · Page 2Linked to original sources

Model for ocular tear film function.

Blepharitis patients have a number of disturbances in their tear film associated with meibomian gland dysfunction that affect evaporation and tear osmolarity. We tested a series of 156 consecutive patients, with a presumed diagnosis of blepharitis, dry eye, or allergic disease, and a series of 72 normals. We compared their tear film characteristics using tear osmolarity, tear volume, tear production (fluorophotometric and Schirmer test), tear turnover (decay constant), tear evaporation, and meibomian gland function evaluated by gland drop-out, expressed lipid viscosity, and volume. Of the 156 patients tested, we found 37 had dry eye, 10 had only allergic disease, 73 had meibomian gland dysfunction and dry eye, and 36 had only meibomian gland dysfunction. We created a model of the relative influence some of these factors had on each other using their correlation coefficients. The highest correlations for osmolarity were Schirmer test (-0.44), lipid volume low (-0.44), lipid viscosity high (0.39), gland drop-out (0.39), and tear evaporation (0.36). With regression analysis we accounted for 47% of the total variation in osmolarity, but only 17% of the variation in tear evaporation. We also present our classification system for blepharitis and dry eye patients based on our measurable physiologic parameters.

Blepharitis↗

Tear film changes associated with normal aging.

We examined a group of normal subjects to evaluate the tear film function by measuring reflex tear capacity using the Schirmer test without anesthetic, steady state tear flow using fluorophotometry, meibomian gland function based on gland drop-out, expressible lipid volume and viscosity, tear loss from evaporation, and tear osmolarity. We found the average tear flow to be 0.19 +/- 0.19 microliters/min, lower than previously measured. The average tear volume was also correspondingly less, 2.74 +/- 2.0 microliters. We found there was a decline associated with advancing age for all parameters except the decay constant and lipid volume. The highest correlations with aging were tear volume (-0.64), Schirmer test (-0.63), and tear osmolarity (0.59). Our results indicate that there is a decline in tear film function throughout life and that tear flow is considerably less than previously estimated.

Adolescent↗

Linkage of posterior polymorphous corneal dystrophy to 20q11.

Posterior polymorphous dystrophy (PPMD) is an autosomal dominant disorder of the cornea that is clinically recognized by the presence of vesicles on the endothelial surface of the cornea. The corneal endothelium is normally a single layer of cells that lose their mitotic potential after development is complete. In PPMD, the endothelium is often multi-layered and has several other characteristics of an epithelium including the presence of desmosomes, tonofilaments, and microvilli. These abnormal cells retain their ability to divide and extend onto the trabecular meshwork to cause glaucoma in up to 40% of cases. A large family with 21 members affected with PPMD was genotyped with short tandem repeat polymorphisms distributed across the autosomal genome. Linkage was established with markers on the long arm of chromosome 20. The highest observed LOD score was 5.54 (theta = 0) with marker D20S45. Analysis of recombination events in four affected individuals revealed that the disease gene lies within a 30cM interval between markers D20S98 and D20S108.

Chromosome Mapping↗

Obstacles to donor eye procurement and their solutions at the University of Iowa.

Shortages in transplantable corneas are common, yet little appears in the medical literature about patterns of tissue donation and factors affecting procurement. We have analyzed data on eye donations and taken measures to improve procurement rates based on our findings. Fifty consecutive Cardiovascular Intensive Care Unit (CVICU) deaths were reviewed to compare the number of transplant-eligible donors to the amount of tissue received. An anonymous survey of 250 house staff and nurses was undertaken to identify obstacles to donor eye procurement. Although 12 of 50 potential donors in the CVICU met transplant eligibility criteria, only 1 became a donor. A required request policy notwithstanding, the most common reason for nonprocurement was failure to make a request. According to the survey, the most significant impediments to making the request were (a) not thinking to ask, (b) unfamiliarity with eligibility criteria, (c) unfamiliarity with enucleation procedures, (d) feeling that someone else should make the request, and (e) reluctance to impose on a grieving family. Very few cited religious reasons or being too busy. Education based on the specific concerns listed in the survey was undertaken. During the 12 months after this initiative, the number of transplantable corneas donated from our facility doubled, as compared with the same period in 1992. Despite required request laws and regulations, failure to request tissue donation is common in our facility and may be common elsewhere. Systematic analysis of obstacles to donor eye procurement and their solutions may help to improve our country's performance in this area.

Corneal Transplantation↗

Basic science and applications of in vivo microscopy.

Confocal microscopy creates a scanned image from a point light source and point detection or a scanning slit to remove scattered light and improve optical resolution. This also results in optical sectioning of tissues. These capabilities can be employed to image structures in the human cornea, in vivo, both for research and for the diagnosis and treatment of human disease. Optical sections, when recombined, can lead to three-dimensional reconstructions from which very useful information is obtained. Investigators have found keratocyte density decreases from anterior to posterior in the stroma of the rabbit cornea. Surface epithelial desquamation can also be studied and the effects of contact lens use can be demonstrated. The instrument is also useful for diagnosing and guiding therapy for some human diseases such as Acanthamoeba keratitis. Colonies of bacteria may also be observed and treatment evaluated in patients with infectious crystalline keratopathy. Confocal microscopy can also image the retina.

Contact Lenses↗

Diagnosis of Acanthamoeba keratitis in vivo with confocal microscopy.

We present eight cases of Acanthamoeba keratitis. In each case; the Acanthamoeba organisms were visualized in the epithelium and anterior stroma using tandem scanning confocal microscopy. The organisms were highly reflective, ovoid, and were 10-25 microns in diameter. The Acanthamoeba organisms in the human corneas were identical in size and shape to Acanthamoeba organisms on an agar plate visualized with the same confocal microscope. Confocal microscopy is a useful method for identifying Acanthamoeba organisms in vivo within the corneal epithelium and anterior stroma.

Acanthamoeba↗

Bilateral herpes simplex virus type 2 keratitis: a clinicopathologic report with immunohistochemical and ultrastructural observations.

This report describes the clinical, histopathologic, ultrastructural, and immunohistochemical findings in two corneal buttons from a 13-year-old girl who developed bilateral progressive corneal stromal opacification during childhood. As determined by light microscopy, both corneal buttons were edematous with a chronic inflammatory infiltrate confined to the deep layers of the stroma. We detected intranuclear eosinophilic inclusions in some epithelial cells. We detected herpesvirus particles in stromal keratocytes and endothelial cells by transmission electron microscopy. Immunohistochemistry studies identified concurrent expression of specific herpes simplex virus type 2 antigen in corneal epithelial cells, in keratocytes in the deep layers of the stroma, and in endothelial cells. The cause of progressive bilateral stromal corneal opacification in this child was herpes simplex virus type 2 keratitis. This condition should be considered in the differential diagnosis of progressive, bilateral corneal opacification in children.

Adolescent↗

Hard-palate mucosa graft in Stevens-Johnson syndrome.

PURPOSE: We evaluated the use of hard-palate mucosa grafts in the treatment of cicatricial entropion and trichiasis associated with Stevens-Johnson syndrome. METHODS: Six patients, two men and four women, were treated with hard-palate mucosa grafts of one or more eyelids with cicatricial entropion, trichiasis, and corneal disease. The follow-up ranged from 19 to 33 months. RESULTS: Visual acuity improved in one of nine eyes and remained stable in the rest. Corneal epithelial disease improved in eight of nine eyes, while in one eye the epithelial defect stabilized. The corneal epithelium of all three corneal transplants remained intact, although one of these patients underwent another corneal transplantation and the other two transplants opacified from rejection. Cicatricial entropion resolved and symblephara improved in all 16 eyelids. Trichiasis resolved or improved in 12 of 16 eyelids and remained stable in the other eyelids. CONCLUSIONS: The chronic relapsing nature of Stevens-Johnson syndrome requires caution in interpreting surgical intervention in the treatment of dysfunctional eyelids. However, hard-palate grafts may be considered for patients with the Stevens-Johnson syndrome and severe ocular surface disease.

Adult↗

The relationship between granular, lattice type 1, and Avellino corneal dystrophies. A histopathologic study.

Three stromal corneal dystrophies (granular, lattice type 1, and Avellino) were recently mapped to a single locus on chromosome 5. This study was conducted to determine if there is histologic evidence to support the allelic relationship suggested by the genetic studies. We examined 23 corneal buttons from the two families with lattice dystrophy and 13 corneal buttons from the two families with granular dystrophy who were involved in the chromosomal linkage studies. In the two families with clinically typical granular dystrophy, one corneal button also contained focal amyloid deposits. In both families with clinically typical lattice dystrophy type 1, we found evidence of granular deposits. The genetic linkage studies demonstrate only that the disease-causing mutations for these three stromal dystrophies share the same genetic locus. However, the evidence of histologic overlap strongly suggests that these dystrophies are caused by mutations within the same gene.

Alleles↗

Three autosomal dominant corneal dystrophies map to chromosome 5q.

The two most common autosomal dominant dystrophies of the corneal stroma are lattice corneal dystrophy type I and granular dystrophy. A third autosomal dominant stromal dystrophy (Avellino) has also been recognized. Chromosome linkage analysis of four families with Avellino dystrophy mapped the disease-causing gene to chromosome 5q. Subsequent linkage analysis of two families with typical lattice dystrophy and two with typical granular dystrophy also revealed significant linkage with the same markers. Thus, each of three clinically and histopathologically distinct phenotypes is independently linked to 5q. The maximum combined lod score using all 114 affected patients was 28.6 with marker D5S393. None of the 14 known human amyloid-associated genes map to chromosome 5.

Alleles↗

Ocular evaporation in meibomian gland dysfunction and dry eye.

BACKGROUND: Secretions from the meibomian gland are believed to be important in reducing ocular surface water evaporation and preventing dry eye. Patients with blepharitis frequently have meibomian gland dysfunction with loss of meibomian glands (drop out). The authors hypothesized that dry eye that often occurs in patients with chronic blepharitis is secondary to increased evaporation associated with gland loss. METHODS: The authors measured the ocular surface water evaporation and tear osmolarity of patients with meibomian gland drop out and patients with gland drop out with a low Schirmer test. These findings were compared with those of a control group. RESULTS: The authors found that eyes with meibomian gland drop out and those with drop out and a low Schirmer test had a significantly higher evaporative rate at 30% relative humidity (average, 49.9 +/- 21 x 10(-7) g/cm2/second, or 0.49 +/- 0.29 microliters/minute evaporative loss per eye, and 59.1 +/- 28 x 10(-7) g/cm2/second, or 0.58 +/- 0.23 microliters/minute, respectively) when compared with those in the control group (average, 14.8 +/- 6 x 10(-7) g/cm2/second, or 0.15 +/- 0.07 microliters/minute [P < 0.05]). There was a significant correlation between evaporative rate and gland drop out (r = 0.522). CONCLUSION: Patients with meibomian gland drop out, and especially those with low tear production by Schirmer test, have an increased risk of dry eye developing through increased evaporation.

Adult↗

Ocular water evaporation and the dry eye. A new measuring device.

We developed a simple device to measure the water evaporation from the ocular surface, and we measured the evaporation rate in 18 normal individuals. We compared this to a group of 15 patients with dry eye from low tear production. We found the normal rate of water evaporation from the ocular surface to be 14.7 +/- 6.4 x 10(-7) g/cm2/s or 0.14 +/- 0.06 microliter/min at 30% relative humidity. For dry eye patients, the rate was significantly increased to 47.6 +/- 20.1 x 10(-7) g/cm2/s or 0.43 +/- 0.19 microliter/min (p < 0.005). Neither group showed any evidence of meibomian gland dysfunction that might have increased evaporation. From these results, we conclude that evaporation is accelerated when tear production decreases and is of sufficient magnitude to exacerbate the dry eye.

Body Water↗

Meibomian gland function and giant papillary conjunctivitis.

We examined 42 contact lens-wearing patients for clinical evidence of giant papillary conjunctivitis and for meibomian gland dysfunction with gland dropout. Fifteen patients were free of clinical signs and symptoms of giant papillary conjunctivitis, whereas 27 had clinical symptoms and evidence of giant papillary conjunctivitis. Patients with giant papillary conjunctivitis had significantly more gland dropout with an average of 0.6 +/- 1.2 gland absent in both lower eyelids compared with 0.2 +/- 0.4 gland absent in patients without giant papillary conjunctivitis. Additionally, the viscosity of meibomian gland excreta was greater in the giant papillary conjunctivitis group. There was no difference in tear osmolarity or in the Schirmer test results between the two groups. These results indicated patients with giant papillary conjunctivitis were more likely to have meibomian gland dysfunction with gland dropout than patients without giant papillary conjunctivitis.

Adult↗

Morphology and movement of corneal surface cells in humans.

We examined the morphology of the corneal surface epithelial cells in 13 eyes of 13 subjects using specular microscopy. We determined cell area, perimeter, and shape comparing the central cornea with the inferior and superior periphery. We found surface epithelial cells are significantly smaller in the central cornea. The cells measured 560 +/- 93 square microns in the central cornea, 850 +/- 135 square microns in the superior cornea and 777 +/- 176 square microns in the inferior cornea (p less than .005). Newly emerged surface cells are smaller and are thought to enlarge with time. We postulate that lid shearing forces are greater in the central cornea and contribute to epithelial cell exfoliation. We further postulate that preferential shearing of central corneal surface cells is an important factor driving the centripetal movement of corneal epithelial cells.

Adult↗

Morphologic effects of contact lens wear on the corneal surface.

We used specular microscopy of the corneal epithelium to examine 29 eyes of 29 patients each wearing one of five different types of contact lenses. We compared these with 24 eyes of 24 age-matched control patients. We found patients with aphakic extended wear soft contact lenses had significantly larger cells (818 +/- 186 microns2) than all other groups; and they were significantly larger than their age-matched control group (573 +/- 174 microns2) (P less than .002). The epithelial cells of extended wear soft contact lens patients (609 +/- 97 microns2) and daily wear rigid gas permeable contact lens patients (613 +/- 103 microns2) were larger than their control group of normal young patients (513 +/- 53 microns2). The cells of daily wear soft contact lens patients (484 +/- 111 microns2) and hard contact lens patients (517 +/- 46 microns2), however, were not different from controls. This study demonstrates a statistically significant shift in mean cell area of corneal epithelial cells in patients wearing some types of contact lenses.

Adult↗

Correlation of full-thickness corneal wound length with endothelial cell loss.

We studied 12 patients who had sustained penetrating corneal lacerations with corneal wound lengths ranging from 1 to 9 mm to determine whether wound size was directly proportional to endothelial cell loss 3 or more months after injury. Endothelial cell counts in the uninjured eye averaged 2973 +/- 330 cells/mm2 (range, 2500 to 3700). In the injured eye, near the wound (less than 2 mm from the wound), the cell counts averaged 1260 +/- 590 cells/mm2 (range, 575 to 2500); away from the wound, where cells appeared healthiest, counts averaged 1619 +/- 544 cells/mm2 (range, 850 to 2750). The average total cell loss near the wound was 1713 +/- 622 cells/mm2 (range, 500 to 2575), vs 1354 +/- 582 cells/mm2 (range, 250 to 2150) away from the wound, compared with the uninjured eye. Cell loss near the wound was not significantly different from that away from the wound. There was a positive correlation between wound length and total cell loss measured both near the wound (r = 0.830) and away from the wound (r = 0.755). Pars plana lensectomy was not associated with detectable additional cell loss. Our results suggest that patients with corneal lacerations sustain significant endothelial cell loss, which correlates closely with wound length, and that patients with larger wounds may be at greater risk for developing corneal decompensation with additional procedures or trauma.

Cell Count↗