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W Richard Green

Publications and source records attributed to W Richard Green.

At least 19 recordsLinked to original sources
PubMed2007

Light-scattering and ultrastructure of healed penetrating corneal wounds.

PURPOSE: To investigate quantitatively for the first time the relationship between light-scattering and ultrastructure of semitransparent scars resulting from penetrating wounds in rabbit cornea. METHODS: Penetrating wounds, 2 mm in diameter, were made in the central cornea and allowed to heal for 3.6 to 4.5 years at which time the rabbits were killed. The scar and cornea thickness outside the scar were measured using ultrasonic pachymetry. Corneas were excised immediately and their transmissivity was measured from 400 to 700 nm. The tissue was then prepared for transmission electron microscopy. Transmission electron micrographs (TEMs) were analyzed to determine fibril positions and radii. Scattering was calculated using the direct summation of fields (DSF) METHOD: RESULTS: Scar thickness averaged 0.26 +/- 0.04 mm, and the scars were flat. Thickness outside the scars averaged 0.40 +/- 0.04 mm. Three scars were moderately transparent, five were less transparent, and one was much less transparent. The wavelength dependence of the measured total scattering cross- section was indicative of the presence of voids (lakes) in the collagen fibril distribution, and lakes were evident in the TEMs. The images showed enlarged fibrils and some showed bimodal distributions of fibril diameters. Calculated scattering was characteristic of that expected from regions containing lakes-a finding consistent with the scattering measurements. CONCLUSIONS: Despite the long healing time, these scars remained highly scattering. A combination of lakes, disordered fibril distributions, and a significant population of enlarged fibrils can explain the scattering. A possible cellular contribution cannot be ruled out.

Animals↗
PubMed2006

Corneal avascularity is due to soluble VEGF receptor-1.

Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.

Animals↗
PubMed2006

Role of electron microscopy in the diagnosis of ocular mucous membrane pemphigoid.

PURPOSE: To evaluate the role of electron microscopy (EM) for the diagnosis of ocular mucous membrane pemphigoid (MMP) among patients with cicatrizing conjunctivitis. DESIGN: Retrospective case series. PARTICIPANTS: One hundred twenty-eight patients with cicatrizing conjunctivitis referred for the evaluation of possible ocular MMP between January 1985 and February 2002 who underwent conjunctival biopsy and evaluation with EM and direct immunofluorescent (DIF) techniques. METHODS: The diagnosis of each patient was based on DIF techniques. The reproducibility of EM readings was measured by assessing intraobserver and interobserver variability. The diagnosis from EM was compared to the DIF diagnosis from the same patient to evaluate the validity of the EM diagnosis. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, and negative predictive value of EM for diagnosing ocular MMP. RESULTS: One hundred twenty-six of 128 conjunctival biopsies were available for evaluation of EM findings. The percent agreement between 2 readings from the same observer was 92%, and the percent agreement between 2 independent observers was 78%. The sensitivity and specificity of EM for the diagnosis of ocular MMP were 51% and 72%, respectively. The positive predictive value of EM for the diagnosis of ocular MMP was 49%. CONCLUSIONS: The reproducibility of EM findings was good as indicated by high percent agreement for both intraobserver and interobserver measurements. However, the sensitivity, specificity, and positive predictive value of EM for the diagnosis of ocular MMP was low. It seems that EM has limited usefulness in the diagnosis of ocular MMP.

Adolescent↗
PubMed2006

The macular hole: histopathologic studies.

OBJECTIVE: To delineate the light and electron microscopic features of tissue removed at the time of macular hole surgery. METHODS: The ocular fluid specimens were concentrated using Millipore filters and stained with a modified Papanicolaou and the periodic acid-Schiff stains in 697 cases. In 92 cases, surgically isolated tissue was processed and examined by electron microscopy. RESULTS: The findings in the specimens studied by the Millipore filter technique included vitreous strands; cellular fragments in 108 cases (13.3%); fibrocellular fragments in 75 (9.2%); and fragments of internal limiting lamina (ILL) of the retina in 104 (12.8%). Findings in the 92 specimens with tissue studied by electron microscopy included native vitreous collagen in 48 cases (52.2%); new collagen in 6 (6.5%); native and new collagen in 1 (1.2%); ILL of the retina in 54 (58.7%); and a variety of cells in 22.5% of cases, including fibrocytes, myofibrocytes, fibrous astrocytes with and without myoblastic features, Mueller cells, retinal pigment epithelium with and without myoblastic features, and inflammatory cells. The organization of the tissue elements included a cellular layer along one surface of a layer of cortical vitreous in 18 cases, cortical vitreous along the inner surface of the ILL of the retina in 10, and cortical vitreous sandwiched between the ILL of the retina and a layer of cells in 9. CONCLUSIONS: Tangential traction induced by fluid movements affecting the cortical vitreous is a major factor in the pathogenesis of idiopathic macular holes. Cellular proliferation is a secondary change seen in 22.2% of cases.

Basement Membrane↗
PubMed2006

An apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation.

Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among the elderly in Western countries. Genetic factors, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors. In this study, we investigated the association between ApoE C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4 isoforms) and age-related macular degeneration (AMD), and the mechanism underlying the association. Genomic DNA was extracted from 133 clinically screened controls, 94 volunteers with a younger mean age, 120 patients with advanced AMD, and 40 archived ocular AMD slides for single nucleotide polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in cultured human retinal pigment epithelium (RPE) cells were tested and serum cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R (E4) distribution differed significantly between AMD patients and controls. ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in the younger controls and 18.8% in the clinically screened controls. The pathologically diagnosed archived AMD cases had the lowest allele frequency of 5%. No significant differences in ApoE158C (E2) distribution were observed among the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong association between AMD and 112R, but not 158C. In vitro studies found that recombinant ApoE suppresses CCL2 and VEGF expression in RPE cells. However, the E4 isoform showed more suppression than E3 in both cases. These results further confirm the association between ApoE112R and a decreased risk of AMD development. The underlying mechanisms may involve differential regulation of both CCL2 and VEGF by the ApoE isoforms.

Adult↗
PubMed2006

Clinicopathologic studies of eyes that were obtained postmortem from four patients who were enrolled in the submacular surgery trials: SST Report No. 16.

PURPOSE: To compare the fundus photographic and fluorescein angiographic features with the histologic findings in eyes from patients enrolled in the Submacular Surgery Trials (SST). DESIGN: Clinical trials with clinicopathologic correlation. METHODS: Eyes that were obtained postmortem from patients who participated in the donor program were processed at the SST Pathology Center and examined histologically; the macular regions were reconstructed topographically with two-dimensional cartography. Fundus photographic and fluorescein angiographic features were correlated with the histopathologic and two-dimensional cartographic findings. RESULTS: The eyes from two patients each from the SST Group N and B Trials were studied. The study eye of one patient that had been assigned randomly to observation contained a subretinal fibrovascular scar that corresponded to a histologic growth pattern of a thick, collagenized subretinal component combined with a subretinal pigment epithelium (subRPE) fibrovascular component. The study eye of the other patient who was assigned randomly to observation showed angiographic occult without classic choroidal neovascularization (CNV) that corresponded to subRPE CNV. The study eye of one patient who was assigned randomly to surgery showed an angiographic surgical defect without CNV and histologic retinal pigment epithelium (RPE)/photoreceptor atrophy that was associated with a thin layer of subRPE CNV. The study eye of the other patient who was assigned randomly to surgery showed an angiographic surgical defect with classic CNV that corresponded to histologic RPE/photoreceptor atrophy that was associated with subRPE fibrovascular tissue and subretinal CNV. Both surgical eyes contained linear breaks in Bruch's membrane that included chevron-shaped breaks. CONCLUSION: Four SST study eyes that were examined postmortem contained CNV. The angiographic patterns and histologic features of the CNV support previous correlations of surgically excised CNV.

Aged↗
PubMed2006

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↗
PubMed2005

Histopathologic and ultrastructural features of surgically excised subfoveal choroidal neovascular lesions: submacular surgery trials report no. 7.

OBJECTIVES: To identify the histologic and ultrastructural features of surgically excised subfoveal choroidal neovascular lesions from patients enrolled in the Submacular Surgery Trials and to compare them with clinical data. METHODS: Surgically excised subfoveal choroidal neovascular lesions from patients enrolled in the Submacular Surgery Trials group N trial (lesion predominantly choroidal neovascularization [CNV] with evidence of classic CNV from age-related macular degeneration), group B trial (lesion predominantly hemorrhagic from age-related macular degeneration), and group H trial (idiopathic subfoveal CNV or subfoveal CNV from ocular histoplasmosis syndrome) between October 1, 1999, and September 1, 2001, were submitted to the pathology center. The lesion growth pattern (subretinal pigment epithelial [sub-RPE], subretinal, combined, or indeterminate) and the cellular and extracellular constituents were classified independently. Demographic, clinical, and fluorescein angiographic characteristics of patients, eyes, and lesions, respectively, were compared with the pathologic features. RESULTS: Of 269 patients assigned to surgery during the 24 months that pathologic specimens were collected, surgical specimens from study eyes of 199 were submitted to the pathology center. Of the 199 routine histologic specimens processed, 144 (72%) were classified as CNV, 51 (26%) as fibrocellular tissue, and 4 (2%) as hemorrhage. The median specimen size was smaller in group H (932 x 208 mum) than in groups N (1980 x 325 mum) and B (1800 x 395 mum). The CNV growth pattern was determined in 91 (46%) of 199 specimens. Of 159 group N and group B lesions, 76 (48%) had an indeterminate growth pattern, 28 (18%) had a sub-RPE growth pattern, and 33 (21%) had sub-RPE and subretinal growth patterns. Of 40 group H lesions, 32 (80%) had an indeterminate growth pattern, 7 (18%) had a subretinal growth pattern, and 1 (2%) had a combined sub-RPE and subretinal pattern. Based on electron microscopy, the most common cellular lesion components were RPE, macrophages, erythrocytes, fibrocytes, and vascular endothelium; the most common extracellular components were 24-nm collagen and fibrin. Basal laminar and linear deposits were found in 80% (40/50) and 16% (8/49) of group N specimens, 66% (43/65) and 5% (3/65) of group B specimens, and 8% (2/26) and 0% (0/26) of group H specimens, respectively. CONCLUSIONS: Most surgically excised subfoveal specimens had evidence of CNV or tissue associated with CNV. The constituents in CNV were consistent with granulation tissue proliferation. The presence of basal deposits in surgically excised specimens suggested a clinical diagnosis of age-related macular degeneration, even when blood was the predominant component of the lesion. Correlation of growth patterns above or below the RPE with fluorescein angiographic patterns of classic or occult CNV was limited because most specimens had insufficient material to determine these patterns.

Aged↗
PubMed2005

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↗
PubMed2005

Periocular petrolatum.

PURPOSE: This report describes the clinical and histopathologic features and discusses the diagnostic difficulties and management of periocular deposition of petrolatum-based materials. METHODS: Excision of orbital and eyelid tissue, tissue processing, and histopathologic examination was performed in patients with deposition of petroleum-based products. Transmission electron microscopy was performed in 3 cases. RESULTS: Between 1983 and 2003, 11 patients were diagnosed with periocular petrolatum deposition, based on clinical history and the characteristic histopathologic features of polymorphic dropout spaces, and varied from a noninflammatory lesion (paraffinoma) to those with an associated granulomatous inflammatory reaction. CONCLUSIONS: The diagnosis of petrolatum deposition can be challenging due to the range of symptoms and variable delay in presentation. Petrolatum products should be avoided during surgery and used judiciously in the postoperative period. To avoid confusion with nonspecific cases of lipogranulomatous inflammation, the terms "ointment granuloma" or "orbital paraffinoma" should be used to refer to patients presenting with orbital/eyelid lesions caused by ointment use.

Adolescent↗
PubMed2005

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↗
PubMed2004

A study of iridectomy histopathologic features of latanoprost- and non-latanoprost-treated patients.

OBJECTIVES: To examine the histopathologic features of iridectomy specimens from patients undergoing glaucoma surgery and to compare histologic abnormalities in a group of patients with a history of latanoprost therapy with those in a group of patients who had no history of prostaglandin therapy (controls). METHODS: Iridectomy specimens and patient history forms were submitted to the central Latanoprost Pathology Center. These were independently examined by 3 ophthalmic pathologists in a masked fashion. Specimens were evaluated for malignant, premalignant, and other changes including differences in levels of pigmentation, degrees of cellularity, inflammation, vascular abnormalities, and changes in the iris pigment epithelium. RESULTS: Specimens were received from 449 patients with a history of latanoprost treatment and 142 patients who had no history of treatment with latanoprost or other prostaglandin analogues. No evidence of malignant or premalignant changes was found. In latanoprost-treated irides, the prevalence of iris freckles was higher (P = .001) than in control irides, as was the combined number of stromal fibroblasts and melanocytes (P<.001). In a subgroup of specimens received through June 2002, there was no significant difference in mean melanocyte counts (P=.35) obtained by immunohistochemical staining techniques between the latanoprost-treated and control groups. CONCLUSIONS: These findings support previous studies indicating that latanoprost-induced eye color changes are due to an increased amount of melanin within the iris stromal melanocytes. The increased numbers of freckles may be a focal manifestation of this effect.

Antihypertensive Agents↗
PubMed2004

Choroidal neovascularization.

PURPOSE: To review clinicopathologic findings of choroidal neovascularization (CNV) in a historical framework with emphasis on pathobiology and correlation with treatment. DESIGN: Selective literature review combined with authors' experience. RESULTS: Choroidal neovascularization represents a stereotypic, nonspecific response to a specific stimulus. Although CNV differs among patients, the general growth patterns are subretinal pigment epithelium (type 1), subretinal (type 2), or combined. Choroidal neovascularization occurs over time in dynamic stages of initiation, active and involutional. Treatments are now being designed based on modern understanding of CNV growth. CONCLUSIONS: Progress continues to be made concerning understanding the pathobiology and treatment of CNV.

Choroidal Neovascularization↗
PubMed2004

Lack of herpes virus DNA in choroidal tissues of a patient with serpiginous choroiditis.

OBJECTIVE: To investigate the role of herpes viruses in the etiology of serpiginous choroiditis. DESIGN: Interventional case report. PARTICIPANT: A 59-year-old male patient with long-term history of serpiginous choroiditis. INTERVENTION: The patient's affected eye was obtained during autopsy. Polymerase chain reaction was performed in the microdissected choroidal tissues. RESULTS: Histopathologic examination demonstrated active inflammation with lymphocytic infiltration of the choroid. No viral DNA was amplified using pairs of herpes simplex virus (HSV) P1/P2 (for HSV-1, HSV-2, Epstein-Barr virus [EBV], cytomegalovirus [CMV] and human herpes virus [HHV]-8), and varicella-zoster virus [VZV] P1/P2 (for VZV, HHV-6, HHV-7) in the infiltrating lymphocytes or choroidal tissues. CONCLUSIONS: The current observation suggests a lack of a role for herpetic viral etiology in the etiopathogenesis of serpiginous choroiditis.

Choroid↗