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R R Allingham

Publications and source records attributed to R R Allingham.

49 records · Page 3Linked to original sources

Dexamethasone-induced ocular hypertension in perfusion-cultured human eyes.

PURPOSE: Glucocorticoid administration can lead to the development of ocular hypertension and corticosteroid glaucoma in a subset of the population through a decrease in the aqueous humor outflow facility. The purpose of this study was to determine whether glucocorticoid treatment can directly affect the outflow facility of isolated, perfusion-cultured human eyes. METHODS: The anterior segments of human donor eyes from regional eye banks were placed in a constant flow, variable pressure perfusion culture system. Paired eyes were perfused in serum-free media with or without 10(-7) M dexamethasone for 12 days. Intraocular pressure was monitored daily. After incubation, the eyes were morphologically characterized by light microscopy, transmission and scanning electron microscopy, and scanning laser confocal microscopy. RESULTS: A significant increase in intraocular pressure developed in 13 of the 44 pairs of eyes perfused with dexamethasone with an average pressure rise of 17.5 +/- 3.8 mm Hg after 12 days of dexamethasone exposure. The contralateral control eyes, which did not receive dexamethasone, maintained a stable intraocular pressure during the same period. The outflow pathway of the untreated eyes appeared morphologically normal. In contrast, the dexamethasone-treated hypertensive eyes had thickened trabecular beams, decreased intertrabecular spaces, thickened juxtacanalicular tissue, activated trabecular meshwork cells, and increased amounts of amorphogranular extracellular material, especially in the juxtacanalicular tissue and beneath the endothelial lining of the canal of Schlemm. The dexamethasone-treated nonresponder eyes appeared to be morphologically similar to the untreated eyes, although several subtle dexamethasone-induced morphologic changes were evident. CONCLUSION: Dexamethasone treatment of isolated, perfusion-cultured human eyes led to the generation of ocular hypertension in approximately 30% of the dexamethasone-treated eyes. Steroid treatment resulted in morphologic changes in the trabecular meshwork similar to those reported for corticosteroid glaucoma and open angle glaucoma. This system may provide an acute model in which to study the pathogenic mechanisms involved in steroid glaucoma and primary open angle glaucoma.

Aged↗

Retroperfusion studies of the aqueous outflow system. Part I: Evaluation of technique using N-ethyl maleimide.

PURPOSE: The goal of this study was to develop a new technique to deliver drugs or other agents to the lumen of the angular aqueous plexus/Schlemm's canal (AAP/SC) while bypassing the trabecular meshwork, thereby gaining insight into AAP/SC inner wall function. METHODS: The anterior chamber is held at a small negative pressure and fluid is allowed to flow retrograde from the limbal vessels, through the collector channels, and into the AAP/SC ("retroperfusion"). Facility measurements are combined with histologic and tracer studies in bovine eyes. RESULTS: (1) Retroperfusion with a saline solution does not alter facility or change outflow pathway morphology; (2) fluid is able to move retrograde from the scleral surface and enter the lumen of the AAP; and (3) retroperfusion with N-ethyl maleimide causes a dose-dependent increase in washout rate and concomitant inner wall breaks. CONCLUSIONS: It is hypothesized that the observed increase in washout is due to leakage of extracellular materials through breaks in the inner wall.

Animals↗

Contact transscleral Nd:YAG laser cyclophotocoagulation. Midterm results.

BACKGROUND: Early reports of both contact and noncontact transscleral Nd:YAG laser cyclophotocoagulation have been encouraging; however, recent evidence indicates a significant incidence of hypotony, visual loss, and phthisis with the noncontact technique with more than 6 months of follow-up. The authors sought to determine the intermediate term effects of contact transscleral Nd:YAG laser cyclophotocoagulation (CYC). METHODS: The authors followed 116 eyes of 114 patients for a minimum of 1 year after treatment of advanced glaucoma with CYC. RESULTS: The mean preoperative intraocular pressure (IOP) of 35.0 +/- 1.0 mmHg decreased to 18.6 +/- 1.1 mmHg (P less than 0.0001) during the average follow-up of 19.0 +/- 0.6 months (range, 12 to 36 months). Intraocular pressure control of 3 to 25 mmHg was achieved in 72%, 3 to 22 mmHg in 65%, and 3 to 19 mmHg in 56% of eyes. Retreatment was required in 31 of the 116 eyes (27%). Intraocular pressure decreased to less than 3 mmHg in 9 eyes and to 0 mmHg in 6 of these 9 eyes. Nineteen eyes, all with initial visual acuity of counting fingers or worse, progressed to no light perception; 17 of 36 eyes (47%) with visual acuity of 20/200 or better lost 2 or more Snellen lines. CONCLUSION: Midterm results of CYC continue to be encouraging but are tempered by a nearly 10% incidence of hypotony or phthisis and the progression of visual loss.

Adolescent↗

The relationship between pore density and outflow facility in human eyes.

The inner wall (IW) endothelial lining of Schlemm's canal was examined in six normal human eyes and four eyes with primary open angle glaucoma (POAG). Outflow facility was measured using constant pressure perfusion at 15 mmHg, eyes were fixed at 15 mmHg, and the IW endothelial lining was isolated and examined by scanning electron microscopy. Pore density, pore diameter, and bulge density were recorded by quadrant, and pore size and density were used to estimate IW endothelial facility, resistance, and hydraulic conductivity (facility per unit area). In POAG eyes, pores were less common (489 +/- 172 vs 1437 +/- 423 pores/mm2; P less than .005) and appeared to be more unevenly distributed than in normal eyes. A regional analysis of pore density (by quadrant) failed to detect a significant difference between quadrants of normal or POAG eyes. Pore density was correlated with measured outflow facility in normal eyes alone (P less than .02) and when normal eyes were pooled with POAG eyes (P less than .001). The percentage of total resistance attributed to the IW endothelium was 5.8% in normals compared to 9.5% in POAG eyes. This indicates there is a greater pressure drop across the IW endothelium in POAG eyes, suggesting that an intrinsic difference in IW endothelial function exists between normal and glaucomatous eyes. However, this difference alone does not account for the decreased outflow facility in POAG eyes. IW endothelial hydraulic conductivity is markedly higher than that of other vascular endothelia. We hypothesize that this may protect the IW endothelial lining of Schlemm's canal from mechanical stress induced by the relatively high rate of transcellular fluid flow.

Aged↗

Probe placement and power levels in contact transscleral neodymium:YAG cyclophotocoagulation.

Transscleral cyclophotocoagulation using a free-running, thermal-mode neodymium:YAG laser with a 2.2-mm-diameter sapphire-tipped contact probe was performed on 27 enucleated human eyes to investigate the effect of probe placement and power levels. We concluded from gross, light, and scanning electron microscopic examinations that a tissue destructive effect on ciliary body and epithelium was produced by positioning the anterior edge of the probe tip 0.5 to 1.0 mm from the visible limbus using a 5- to 9-W power setting for 0.7 second. An 11-W power setting resulted in extensive loss of anatomic integrity of the ciliary body. Limbal probe placement produced significant iris and lens damage while positioning the probe 1.5 mm posterior to the limbus affected primarily pars plana. Damage to the sclera was not observed using this method of cyclophotocoagulation.

Aged↗

Contact transscleral continuous wave neodymium:YAG laser cyclophotocoagulation.

Advanced glaucoma in 140 eyes of 136 patients was treated with contact transscleral continuous wave neodymium:YAG (Nd:YAG) laser cyclophotocoagulation (CYC) with a sapphire-tipped probe. The anterior edge of the probe was placed 0.5 to 1.5 mm posterior to the limbus, using 7 to 9 W of power for 0.7 seconds with 32 to 40 applications, sparing the 3 and 9 o'clock meridians. Patients were studied prospectively. The mean preoperative intraocular pressure (IOP) of 36.7 +/- 0.97 mmHg decreased to 21.2 +/- 0.99 mmHg (P = 0.004) after treatment (mean follow-up, 3.2 +/- 0.35 months) for a mean decrease in IOP of 15.5 +/- 1.21 mmHg and a mean percent decrease of 39%. Forty-one eyes were followed 6 or more months (mean, 6.7 +/- 0.25 months). The CYC reduced IOP to 25 mmHg or less in 71% of eyes, to 22 mmHg or less in 62% of eyes, and to 19 mmHg or less in 49% of eyes. Maximum lowering of IOP occurred 1 week to 1 month after treatment and remained at that level through 6 months of follow-up. Retreatment was required in 11% of patients; only one patient was retreated more than once. Four patients treated with 9 W of power developed IOPs below 5 mmHg; two of these patients had an IOP of 0 mmHg. Other complications of therapy were minimal, and patients had little pain. There was no significant change in visual acuity. Early results of this newly available therapy are encouraging.

Adolescent↗

Topical aminocaproic acid significantly reduces the incidence of secondary hemorrhage in traumatic hyphema in the rabbit model.

Systemically administered aminocaproic acid has been shown to reduce the incidence of secondary hemorrhage after traumatic hyphema. To date, no topical treatment has been shown to be effective in reducing the incidence of rebleeding in a double-masked study. Experimentally induced traumatic hyphemas in the rabbit model were treated with topical placebo gel (4% carboxypolymethylene gel only) or carboxypolymethylene gel with amino-caproic acid (treated group) in a double-masked fashion and were compared with untreated controls (control group). In both the control and placebo groups, there was a 33% rebleed rate. The treated eyes had a 10% rebleed rate that is statistically significant. The topically applied aminocaproic acid gel appears to be well tolerated locally without evidence of systemic toxicity. This study indicates that topical aminocaproic acid may be an effective alternative to systemic treatment to reduce the incidence of secondary hemorrhage in traumatic hyphema.

Acrylic Resins↗

Trabeculectomy with resection of ciliary processes in glaucoma following scleral buckling.

We report a case of glaucoma following scleral buckling that required filtering trabeculectomy. Despite anterior entry to the anterior chamber, swollen ciliary processes were incarcerated in the sclerostomy site, blocking aqueous flow. Resection of the occluding ciliary processes resulted in restoration of aqueous flow through the sclerostomy. This case demonstrates that anterior rotation of the ciliary body and processes plays an important role in the pathogenesis of glaucoma following scleral buckling operation.

Aged↗

Topically applied aminocaproic acid concentrates in the aqueous humor of the rabbit in therapeutic levels.

Systemically administered aminocaproic acid, used to reduce the incidence of secondary hemorrhage in traumatic hyphema, has been shown to accumulate in the aqueous humor of rabbits in a dose-dependent manner. Eight topical preparations of aminocaproic acid were studied to determine aqueous humor concentrations. The vehicles studied included the following: sodium chloride, 0.85 g/dL; polyvinyl alcohol, 1.4 g/dL; hydroxypropyl methylcellulose, 0.4 g/dL; benzalkonium chloride, 0.01 g/dL; ethylenediamine tetraacetic acid disodium, 0.01 g/dL; dimethyl sulfoxide, 11 and 39.6 g/dL; and carboxypolymethylene, 4 g/dL. All contained 735 g/L of aminocaproic acid except for dimethyl sulfoxide (39.6 g/dL) and carboxypolymethylene (4 g/dL), which contained 238 and 600 g/L of aminocaproic acid, respectively. Aqueous humor and plasma samples were assayed for aminocaproic acid content following topical administration. Aqueous humor concentrations of aminocaproic acid ranged from undetectable (less than 0.01 mg/dL) to 5.75 mg/dL. Plasma concentrations ranged from undetectable (less than 0.01 mg/dL) to 9.85 mg/dL. Polyvinyl alcohol (1.4 g/dL) and carboxy polymethylene (4 g/dL) provided the highest aqueous humor aminocaproic acid concentrations. The aqueous humor levels with topical aminocaproic acid administration were comparable with those achieved by systemic administration. Plasma drug levels with topical aminocaproic acid were between 5% and 33% of levels achieved by systemic aminocaproic acid. This study demonstrates that aminocaproic acid can be effectively delivered into the anterior chamber of rabbits by topical application.

Acrylic Resins↗

Adult-onset primary open angle glaucoma does not localize to chromosome 2cen-q13 in North American families.

Glaucoma is one of the leading causes of irreversible blindness in the world and is characterized by elevated intraocular pressure, optic nerve atrophy, and progressive visual field loss. Primary open angle glaucoma (POAG) is the most common subtype of glaucoma in the United States. Recently, Stoilova and coworkers [Genomics 1996;36:142-150] identified a locus for POAG on chromosome 2 (2cen-q13) in families primarily located in the United Kingdom. We examined families with POAG identified within the US for linkage to the 2cen-q13 locus. A total of 18 families with POAG were used in the analysis. Of 77 family members, 46 were classified as affected and 31 were either glaucoma suspects or considered normal. Eight highly polymorphic and informative markers flanking and distributed throughout the region were used. Parametric lod score analysis was performed using both a dominant and recessive low penetrance or 'affecteds-only' model. Multipoint affected sibpair exclusion mapping was also performed. Lod score (both models) and sibpair analysis excluded linkage of the POAG phenotype to the 2cen-q13 region in these families. These data suggest that the chromosome 2cen-q13 locus does not explain a substantial amount of genetic variation in familial POAG.

Adult↗

Follow-up of argon laser trabeculoplasty: is a day-one postoperative IOP check necessary?

BACKGROUND AND OBJECTIVES: To evaluate the benefit of measuring the intraocular pressure (IOP) on the first postoperative day after argon laser trabeculoplasty (ALT). PATIENTS AND METHODS: We retrospectively reviewed 407 ALT procedures with perioperative apraclonidine performed on 226 patients between January 1991 and December 1993. Data analyzed included type of glaucoma, extent of treatment, whether the procedure was initial or repeat, laser parameters, and IOP preoperatively and at 1 hour, 1 day, and 1 month postoperatively. RESULTS: The percentage of patients with an IOP rise of greater than 3 mm Hg at 1 hour, 1 day, and 1 month following ALT was 11.3%, 4.2%, and 5.2% respectively. The incidence of IOP elevations greater than 10 mm Hg was 2.2%, 1.0%, and 1.5% at 1 hour, 1 day and 1 month, respectively. Of 17 cases with an IOP elevation greater than 3 mm Hg at 1 day, four eventually required a trabeculectomy. However, there were no consistent factors that distinguished which cases with elevated IOP at 1 day ultimately needed further therapy, nor did the 1-day postoperative examination predict which patients would have IOP elevation at 1 month. CONCLUSION: IOP 1 day after ALT is rarely elevated and does not correlate with IOP elevation at 1 month. Therefore, an IOP check at 1 day is not felt to be necessary for most patients.

Adrenergic alpha-Agonists↗