Biomedical subjects

I J Constable

Publications and source records attributed to I J Constable.

At least 91 records · Page 5Linked to original sources

PubMed1995

Visual outcome of excimer laser photorefractive keratectomy for myopia. A comparison of three laser delivery systems in Australia.

PURPOSE: To compare the performance of the three excimer laser delivery systems in correcting myopia. METHODS: The first generation excimer laser systems produced by Summit, VISX and LEI were examined. The first 40 consecutive eyes with six-month refractive results were selected from the LEI centre. Forty consecutive eyes, matched for age and attempted corrections, were then selected from each of the Summit and VISX centres. The postoperative visual results were examined retrospectively and compared among the three groups. RESULTS: At six-month follow-up, the mean and standard deviation of the spherical equivalent refraction were +0.27 (SD, 0.65) dioptre in the Summit group, -0.33 (SD, 0.83) dioptre in the VISX group and -0.62 (SD, 0.89) dioptre in the LEI group (P = 0.0001, ANOVA). Thirty-five eyes (88%) in the Summit group, 33 eyes (83%) in the VISX group and 28 eyes (70%) in the LEI group achieved corrections within 1 dioptre of intended corrections (P = 0.131, chi 2 test). Four eyes (10%) in the Summit group, two eyes (5%) in the VISX group and one eye (3%) in the LEI group were overcorrected by more than 1 dioptre at six-month follow-up. Unaided visual acuity (Snellen equivalent) was 6/12 or better in 37 eyes (93%) in the Summit group, 34 eyes (85%) in the VISX group and 34 eyes (87%) in the LEI group (data missing in one eye). Loss of one or more lines of best corrected visual acuity (Snellen equivalent) was found in 6 of 39 eyes (15%) in the Summit group, 10 of 40 eyes (25%) in the VISX group and 4 of 36 eyes (11%) in the LEI group (P = 0.258, chi 2 test). Regression between one and six month follow-up differed significantly (P = 0.001, ANOVA) among the groups, with the mean of -1.25 (SD, 0.94) dioptres in the Summit group, -0.59 (SD, 1.01) dioptre in the VISX group and -0.40 (SD, 0.99) dioptre in the LEI group. CONCLUSIONS: Statistically comparable results were found in the three groups in terms of refraction and visual acuity six months after myopic photorefractive keratectomy. No statistical differences were found between the groups in terms of significant overcorrection or loss of best corrected acuity. The group treated using the Summit system demonstrated significantly greater regression than the other groups, necessitating larger initial hyperopic shifts.

Adult↗

PubMed1995

Melanin-containing hydrogel intraocular lenses: a histopathological study in animal eyes.

Poly(2-hydroxyethyl methacrylate) hydrogel intraocular lenses, containing adrenochrome-melanin, were manufactured and implanted in animal eyes in order to assess the effect of melanin upon (a) biocompatibility of implants with the eye tissues, and (b) fibrous proliferation of lens epithelium responsible for the opacification of the posterior capsular membrane. An equal number of control lenses were also implanted. The animals were followed up for durations up to two years, and a detailed histopathological examination of the eyes was performed subsequent to their enucleation. The postoperative complications were minor and probably caused by surgical trauma. The study failed to give any indication of the postulated antiproliferative activity of adrenochrome-melanin since minimal capsular opacification occurred in the operated eyes, regardless of the presence of melanin.

Animals↗

PubMed1995

The influence of cerebrospinal fluid pressure on the lamina cribrosa tissue pressure gradient.

PURPOSE: To measure the tissue pressure gradient through the optic disk and to determine the relationship between intraocular, cerebrospinal fluid, and retrolaminar tissue pressures. The relationship of optic nerve subarachnoid space pressure to intracranial cerebrospinal fluid pressure also was explored. METHODS: Micropipettes coupled to a pressure transducer were passed through pars plana and vitreous to enter the optic disk in the anesthetized dog. Using a micromanipulator, pipettes penetrated the optic disk in steps while pressure measurements were taken. In some animals, pipettes also were passed into the optic nerve subarachnoid space. Lateral ventricle cerebrospinal fluid pressure, intraocular pressure, and arterial blood pressure were measured concurrently, and the effect of raising CSF pressure was explored. RESULTS: Retrolaminar tissue pressure was largely dependent on the surrounding cerebrospinal fluid pressure, which was on average 8.6 +/- 3.5 mm Hg (SD, n = 8) higher, and was independent of intraocular pressure. Most (85% +/- 15% [SD, n = 8]) of the pressure drop between intraocular pressure and retrolaminar pressure occurred across the anterior 400 microns of disk tissue. When the intraocular pressure was 21 mm Hg and the cerebrospinal fluid pressure was zero, retrolaminar tissue pressure averaged 7 mm Hg and the translaminar pressure gradient was 3.08 +/- 0.29 mm Hg/100 microns tissue (SD, n = 3). Optic nerve subarachnoid space pressure was equivalent to lateral ventricular pressure. CONCLUSIONS: These results show that cerebrospinal fluid pressure largely determines retrolaminar tissue pressure; hence, along with intraocular pressure, it is of major importance in setting the translaminar tissue pressure gradient. Results also demonstrate hydrostatic continuity between the optic nerve subarachnoid space and the lateral ventricle. That the translaminar pressure gradient can vary independently of intraocular pressure may be of importance in understanding the pathophysiology of glaucoma.

Animals↗

PubMed1994

Interpenetrating polymer network (IPN) as a permanent joint between the elements of a new type of artificial cornea.

The combination at the interface between two chemically identical polymers was investigated by light and electron (scanning, transmission) microscopy. The polymers constitute elements of a new type of artificial cornea in which the peripheral skirt is made from spongy poly(2-hydroxyethyl methacrylate) (PHEMA) and the central optical zone from homogeneous, transparent PHEMA. Their two-phase combination along the boundary fulfill formally the requirements for an interpenetrating polymer network (IPN). The procedure for the manufacture of prosthesis was described in detail. Thin and ultrathin sections excised from the interface region were investigated using microscopic techniques. Light microscopy allowed the measurement of the diffusion path length of transparent PHEMA into sponge, which was approximately 0.5 mm. Transmission electron microscopy revealed a cellular-like morphology as well as larger segregated zones, which indicated network interpenetration on a molecular level and also a relatively poor miscibility of the two polymers despite their identical chemical structure. The latter was interpreted as a result of the submicroscopic restraints imposed by polymer I (sponge) upon polymer II. This study provides evidence that the interface combination of the prosthetic elements should be regarded as a gradient homo-IPN. This system offers a union between elements much stronger than those previously reported in artificial corneas.

Biocompatible Materials↗

PubMed1994

Kinetic studies on phagocytosis and lysosomal digestion of rod outer segments by human retinal pigment epithelial cells in vitro.

Using novel methodology, this study describes the kinetics of rod outer segment (ROS) phagocytosis and digestion by human retinal pigment epithelial (RPE) cells in vitro and examines the effect of certain lysosomal enzyme inhibitors on ROS digestion in these cells. Human RPE cells displayed saturation of phagocytosis with respect to both ROS concentration and time. While surface-binding and ingestion phases of ROS phagocytosis saturated after 24-36 h, the rate of ROS digestion reached a maximal level within 24 h. Increasing the concentration of zinc in the culture medium from 1.9 to 100 microM had no significant effect on ROS digestion. The effects of swainsonine (an alpha-mannosidase inhibitor), pepstatin (an aspartic protease inhibitor), and leupeptin (a cysteine protease inhibitor) were also examined. At 6 h, ROS digestion was reduced 27.3 +/- 15.3% by swainsonine, 69.4 +/- 20.9% by pepstatin, and 77.0 +/- 14.4% by leupeptin. The effect of these inhibitors declined with increasing time. This study is the first to demonstrate the functional importance of cysteine and aspartic proteases in the digestion of ROS by RPE cells in vitro.

Animals↗

PubMed1994

Automated extraction and quantification of macular drusen from fundal photographs.

The objective quantification of drusen (and other macular lesions) should have applications epidemiologically, in the study of the natural history of drusen, and with such instruments as the scanning laser ophthalmoscope. The automated extraction of drusen from photographs is technically difficult because of uneven macular reflectance, and the confusing pattern of darker vessels. We have developed a method using an IBM personal computer, an image digitising board and specially written software. Once the image is digitised, no further input from the operator is necessary. We present the results of manual counting versus automated counting on a small series of patients with drusen. The automated technique is highly reproducible, and will calculate the retinal area occupied by drusen. The area and numbers of drusen can be compared over time, giving an index of progression. Hard drusen are fairly well detected, but the detection of soft drusen with their lower contrast remains a problem. The technique cannot distinguish between drusen and other pale lesions (e.g., atrophic retinal changes).

False Positive Reactions↗

PubMed1994

193 nm excimer laser sclerostomy in pseudophakic patients with advanced open angle glaucoma.

A modified open mask system incorporating an en face air jet to dry the target area during ablation and a conjunctival plication mechanism, which allows ab externo delivery of the 193 nm excimer laser without prior conjunctival dissection, has been developed to form small bore sclerostomies accurately and atraumatically. Full thickness sclerostomies, and sclerostomies guarded by a smaller internal ostium can be created. A pilot therapeutic trial was conducted in pseudophakic patients with advanced open angle glaucoma. Six full thickness sclerostomies (200 microns and 400 microns diameter) and three guarded sclerostomies were created in nine patients by 193 nm excimer laser ablation (fluence per pulse 400 mJ/cm2, pulse rate 16 Hz, air jet pressure intraocular pressure +25 mm Hg). After 6 months' follow up, intraocular pressure was controlled (< or = 16 mm Hg) in eight of the nine patients (6/9 without medication). Early postoperative complications included hyphaema (trace--2.5 mm) (6/9), temporary fibrinous sclerostomy occlusion (4/9), profound early hypotony (all patients without fibrinous occlusion), and suprachoroidal haemorrhage in one case. Conjunctival laser wounds were self sealing. Small bore laser sclerostomy procedures are functionally equivalent to conventional full thickness procedures, producing early postoperative hypotony, with an increased risk of suprachoroidal haemorrhage in association with this. Further research is required to improve control over internal guarding in excimer laser sclerostomy before clinical trials of this technique can safely proceed.

Cataract Extraction↗

PubMed1994

Synthetic polymers as materials for artificial vitreous body: review and recent advances.

In spite of a century of recorded attempts to replace the vitreous body of the eye with a foreign material, there is no permanent substitute currently available, and the success of some materials as temporary substitutes is still very limited. Among the large number of materials proposed or tested as vitreous substitutes, synthetic polymers have been episodically considered during the past four decades. This article will review these attempts, their outcomes, and recent progress in this field. There were only seven synthetic polymers and a few semisynthetic polymers (modified biopolymers) so far proposed or tested as vitreous substitutes. It appears that probably a synthetic hydrogel with very high water content would eventually be the material of choice for a permanent vitreous substitute, but the ideal material has not yet been found.

Animals↗

PubMed1994

Significance of Bruch's membrane in the creation of iatrogenic chorioretinal venous anastomosis.

Iatrogenic retinal to choroidal vein anastomoses, as a method of bypassing retinal venous occlusions has been reported in dogs in which Bruch's membrane is poorly formed. In order to determine whether chorioretinal venous anastomoses can be induced in an animal with a Bruch's membrane that is well developed as in humans, pigmented rats were chosen. A high intensity, small spot size argon green laser beam of 514 nm was used to induce the anastomosis. Three out of 5 rat eyes developed a retinal vein to choroidal vein anastomosis. The success rate of iatrogenic retinal to choroidal vein anastomoses in the rat was comparable to that obtained in the dog. This study suggests that Bruch's membrane was not significant in the creation of an iatrogenic chorioretinal venous anastomosis.

Anastomosis, Surgical↗

PubMed1994

Detection and possible functions of a cysteine protease involved in digestion of rod outer segments by retinal pigment epithelial cells.

PURPOSE: To investigate the presence and role of a recently cloned cysteine protease (cathepsin S) in the digestion of rod outer segments (ROS) by cultured retinal pigment epithelial (RPE) cells. METHODS: RPE cell cultures were established from eye bank donor eyes. Total RNA was extracted from freshly harvested cultures, and after reverse transcription, the cDNA was subjected to polymerase chain reaction (PCR). Cathepsin S (Cat S) mRNA translation was inhibited by antisense oligonucleotides, and the effect of inhibition on the accumulation of fluorescent debris was examined. The activity of cysteine and aspartic proteases in ROS-challenged RPE cell cultures was inhibited by leupeptin and pepstatin, respectively. The accumulation of autofluorescent debris within RPE cells was measured by a fluorophotometric flow cytometer. The presence of phagosomes in antisense DNA-inhibited and control cultures was demonstrated by electron microscopy. RESULTS: The expression of Cat S in RPE cells was demonstrated by RNA-PCR. Using antisense oligonucleotide-mediated-specific inhibition of Cat S, a significant ROS-derived increase in autofluorescence was detected within the RPE cells when they were compared with the unchallenged control cultures and cultures in the presence of ROS and sense oligonucleotides. Electron microscopy demonstrated the presence of a large number of phagosomes that enveloped structures similar to ROS. The accumulation of autofluorescent debris was also demonstrated in cysteine protease-inhibited, ROS-challenged RPE cultures, but it was not detected with aspartic protease inhibition. CONCLUSIONS: The expression of Cat S in RPE cells and the accumulation of an autofluorescent debris in cultures in which cysteine proteases or Cat S activity is inhibited suggest a key role for this enzyme, either in the ROS digestion process or in the activation of cathepsin D, the major lysosomal enzyme present in RPE cells.

Animals↗

PubMed1994

Symptoms and signs of retinal disease.

Of all the diseases of the eye, the retinal disorders are perhaps the most frequently misdiagnosed by the general medical community. The content of this article is restricted to retinal diseases and the importance of symptoms and signs in their accurate diagnosis.

Fluorescein Angiography↗

PubMed1993

A quantitative study of the lateral spread of Müller cell responses to retinal lesions in the rabbit.

A wide variety of retinal pathology is associated with an increase in Müller glial cell expression of glial fibrillary acidic protein (GFAP). In this study the time course and spatial spread of the Müller cell GFAP response following argon laser photocoagulation lesions was examined in wholemounted rabbit retina. At 24 hours single focal lesions were surrounded by GFAP positive Müller cell end feet which declined in density with distance but extended as far as 2-3 mm from the lesion. The Müller cell reaction reached a maximal spread of 4-5 mm at 14 to 21 days and had started to contract by 30 days, leaving a core of GFAP positive processes immediately around the lesion site at 60 days. This zone of spread was much larger than the area of disrupted pigment epithelium. Isodensity plots did not reveal any correlation with the trajectory of retinal ganglion cell axons. The spread of reaction was more confined for lesions within the visual streak than in the dorsal or ventral retinal periphery. Multiple lesions within a focal region of retina resulted in a greater density of GFAP reactive end feet with a corresponding greater spread. However, when five to ten lesions were made in a horizontal row, the Müller cells over the entire retina became GFAP immunoreactive. This pan-retinal reaction took several days to spread, peaked at 7-14 days, and contracted back to the primary lesion sites by 2 months. This spread of Müller cell reactivity may be triggered by the diffusion of substances released by injury or it may be due to direct cellular communication. The extensive indirect effect on Müller cells of laser irradiation might be an important component of the clinical effect of laser photocoagulation and indicates a long distance communication mechanism between retinal glia which is poorly understood. This study also shows the importance of the time at which the Müller cell response is assessed.

Animals↗

PubMed1993

Severe corneoscleral infection. A complication of beta irradiation scleral necrosis following pterygium excision.

OBJECTIVE: To assess the precipitating factors, clinical course, and treatment of 11 cases of severe intraocular infections of radionecrosis after pterygium excision in an attempt to minimize the devastating ocular sequelae. DESIGN AND SETTING: From the database of cases of radionecrosis at Royal Perth (Australia) Hospital and Lions Eye Institute, Perth, we identified 11 cases of severe intraocular infection complicating radionecrosis. We reviewed the case notes and the available radiotherapy records (n = 8). PATIENTS: Eleven patients admitted during an 8-year period. RESULTS: Mean (+/- SD) dose of radiotherapy was 22.7 +/- 1.0 Gy and mean latency period, 14.45 +/- 2.5 years. Among the six proven bacterial cases, Pseudomonas was identified in four, Staphylococcus aureus in one, and Streptococcus pneumoniae was involved in one bilateral case. Among the four fungal cases, Petriellidium boydii was indicated in two, and Fusarium and Scedosporium inflatum in one each. The condition may remain undiagnosed for some time and mimic a posterior scleritis, serous retinal detachment, or pseudotumor. INTERVENTIONS: Early débridement and culture; close microbiological assistance; and systemic antimicrobials for a prolonged period. Perforation or incipient perforation necessitated penetrating keratoplasties in seven patients and repeated keratoplasties in three. MAIN OUTCOME MEASURES: The use of radiotherapy following pterygium excision should be limited and only low doses used. Ulcer beds and calcific plaques at sites of radionecrosis should not be directly covered without first performing adequate sterilization. Removal of plaques may precipitate sepsis; ulcer beds and plaques harbor infective agents. CONCLUSION: Severe radionecrosis may expose a patient to a lifelong risk of intraocular sepsis and profound visual morbidity. Conjunctival autografting is a safer method to reduce recurrence rate after pterygium excision.

Aged↗

PubMed1993

Improved excimer laser photorefractive keratectomy system.

An improved 193 nm excimer laser photorefractive keratectomy system is described here. The delivery system was optimised to produce a smooth keratectomy bed, to minimise the healing response, and to reduce the regression of the refractive result. A spatial filtering system was used to smooth the energy distribution within each pulse, and the iris was adjusted for every pulse, to eliminate steps and other irregularities from the keratectomy profile. An image rotator was used to average out any remaining non-uniformities in the energy distribution. The results from the first 39 eyes treated with this laser system with a maximum follow-up of 18 months, are summarised. No epithelial healing problems were noticed, and little or no loss of corneal clarity was noted at any stage during healing. Twenty of the keratectomy procedures were normally sighted myopic corrections, with a maximum follow-up of 5 months. Minimal regression of the refractive correction was seen during the first 8 weeks.

Argon↗

PubMed1993

Horizontal cells of the normal and dystrophic rat retina: a wholemount study using immunolabelling for the 28-kDa calcium-binding protein.

Immunocytochemistry with a monoclonal antibody against the 28-kDa calcium-binding protein (28-kDa CaBP) was used to study horizontal cells in both congenic control (RCS-rdy+) and dystrophic (RCS) 3-month-old rat retina. We found that horizontal cells in the RCS-rdy+ rat retinas were distributed evenly from the centre to the peripheral retina with a mean density of 783 cells mm-2. Cell size ranged between 6.5-12.5 microns in diameter with a mean of 8.87 microns. Individual cell processes could not be followed readily, however they formed a narrow plexus within the outer plexiform layer with the primary dendrites extending radially from each cell soma in an organized manner. In the RCS rat, by contrast, the horizontal cell processes were more disorganized than in the congenic controls. The degree of disorganization varied across the retina. In the posterior pole, where all outer layers had been lost, many processes were grossly swollen along their length and at the tips. The cell somas were also distributed more widely in the depth of the retina. In the peripheral retina, where a debris layer was still present, the processes were less swollen but they extended abnormally widely in depth. Despite the disorganized structure the mean and range of cell size (9.23 microns, 5.5-15.5 microns), and cell density (796 cells mm-2) were similar to that of the control RCS-rdy+ animals. These findings indicate that in dystrophic retinas beyond a certain stage of degeneration the horizontal cells become abnormal in their structure but are present at a normal density and the somas are not grossly swollen or shrunken.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

193-nm excimer laser sclerostomy using a modified open mask delivery system in rhesus monkeys with experimental glaucoma.

Excimer laser sclerostomy is a new glaucoma filtration procedure in which the argon fluoride excimer laser at 193 nm is delivered ab externo through a modified open mask system incorporating an en-face air jet to dry the target area and preserve hemostasis during ablation and a conjunctival plication mechanism, which allows the conjunctival and scleral wounds created by through-and-through ablation to separate once the mask is removed. No preparatory dissection of the conjunctiva is required. Five 200-microns and five 500-microns sclerostomies were formed by ablation at a pulse repetition rate of 20 Hz and a fluence per pulse of 400 mJ/cm2 in fellow eyes of five rhesus monkeys with experimental glaucoma. Overall, seven of the ten eyes attained a functional result, with intraocular pressures remaining below 21 mmHg for 6 +/- 1 days and rising to the pre-operative level after 10 +/- 3 days without adjunctive antifibroblast medication. The duration of filtration for 200-microns and 500-microns sclerostomies was similar, and parallels that previously observed for posterior lip sclerectomy in the same animal model. The three eyes with no functional result all had incorrectly positioned sclerostomies. Choroidal detachment and significant shallowing of the anterior chamber did not occur. Excimer laser sclerostomy appears to be a viable technique for filtration, provided that mask placement is accurate.

Animals↗

PubMed1993

Poly(2-hydroxyethyl methacrylate) sponges as implant materials: in vivo and in vitro evaluation of cellular invasion.

The pore size and the in vivo behaviour of four poly(2-hydroxyethyl methacrylate) sponges were investigated. The sponges were synthesized by polymerization of monomer in 70, 80 and 90 wt% water, respectively. In one of the formulations, a high amount of initiator was added. The average pore diameter was calculated with Ferry's equation and the results compared to those obtained by examination of samples using environmental scanning electron microscopy. The use of the equation greatly underestimated the size of pores. We also showed that the pores in polymers obtained in 70 wt% water were not interconnected, whilst the pores in polymers obtained in 80 and 90 wt% water, respectively, were larger and interconnected throughout the polymer. When implanted subcutaneously in rabbits, only the latter polymers allowed invasion and proliferation of cells. Penetration and proliferation of cells in these sponges were also assessed by an in vitro method using cultured human fibroblasts. The procedure included the overlaying of a glass plate covered by confluent cultured cells on to the surface of polymer impregnated with collagen. The depth of migration and number of sections needed to be cut to count a fixed number of invading cells were measured after incubation for 2 wk and used as indicators in comparing the ability of various sponges to allow cellular invasion. The assay showed that more cells invaded a hydrogel sponge produced in 80 wt% water than one produced in 90 wt% water. It also showed that the cut polymer surfaces allowed a greater cellular invasion than the moulded ones.

Animals↗

PubMed1993

Excimer laser sclerostomy: the in vitro development of a modified open mask delivery system.

The argon fluoride (ArF) excimer laser at 193 nm ablates the ocular tissues with a new order of precision and virtually no adjacent damage. A glaucoma filtration operation has been designed in which small-bore sclerostomies are created using the ArF excimer laser delivered through an open mask. The mask plicates the conjunctiva at the limbus prior to ablation. Removing the mask at the end of the procedure allows the conjunctiva to relax back to its original position, separating the conjunctival and scleral wounds. Formal conjunctival dissection is thus avoided. Feasibility studies in cadaver pig eyes, using a fluence per pulse of 400 mJ/cm2 and a pulse repetition rate of 20 Hz, indicate that sclerostomies of 300 microns diameter can be reliably formed if an en-face air jet is built into the mask to raise the pressure in the target area, preventing aqueous flooding.

Animals↗