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[Influences of portal pressure change on intestinal permeability in patients with portal hypertension].

OBJECTIVES: To investigate intestinal permeability in patients with portal hypertension and to search for a relationship with portal pressure. METHODS: Twenty patients with portal hypertension were divided two groups (A, B), 10 patients per group. In group A patients were treated with combined TIPS and modified Sugiura. In group B, patients were treated with modified Sugiura only. Intestinal permeability was assessed before operation, two weeks after TIPS, and two weeks after modified Sugiura, and 20 healthy control subjects were also assessed. RESULTS: Intestinal permeability was significantly higher in patients with portal hypertension than in healthy controls (0.132 +/- 0.110 vs. 0.032 +/- 0.018, P < 0.01). In group A, portal pressure and intestinal permeability decreased two weeks after TIPS (P < 0.05) and no obvious change was noted two weeks after modified Sugiura; but they were significantly lower than those before TIPS (P < 0.05). In group B intestinal permeability was not different before and after operation. Intestinal permeability in group A was not different from that in group B before treatment, but significantly lower after modified Sugiura (P < 0.05). Portal pressure was significantly correlated with intestinal permeability (r = 0.627, P < 0.01). CONCLUSIONS: This study shows that combined TIPS and modified Sugiura can lower portal pressure and intestinal permeability, and enhance the therapeutic efficacy on portal hypertension.

Female↗

Influence of portal pressure change on intestinal permeability in patients with portal hypertension.

OBJECTIVE: To investigate intestinal permeability in patients with portal hypertension and its relationship with portal pressure. METHODS: Twenty patients with portal hypertension were divided into two groups (A, B), 10 patients per group. In group A, patients were treated with combined transjugular intrahepatic portosystemic shunt (TIPS) and modified Sugiura. In group B, patients were treated with modified Sugiura only. Intestinal permeability was assessed before operation, two weeks after TIPS, and two weeks after modified Sugiura; 20 healthy control subjects were also assessed. RESULTS: Intestinal permeability was significantly higher in the patients than in the control group (P<0.01). In group A, portal pressure, intestinal permeability decreased two weeks after TIPS (P<0.05), and no obvious change was noted two weeks after modified Sugiura; but they were significantly lower than those before TIPS (P<0.05). In group B, intestinal permeability was not different before and after operation. Intestinal permeability in group A was not different from that in group B before treatment, but significantly lower after modified Sugiura (P<0.05). Portal pressure was significantly correlated with intestinal permeability (r=0.627, P<0.01). CONCLUSIONS: This study shows that combined TIPS and modified Sugiura can lower portal pressure and intestinal permeability, and enhance the therapeutic efficacy on portal hypertension.

Adult↗

Dentin permeability: effects of crown preparation.

Sequential crown reductions of extracted human teeth were made to evaluate both regional differences in dentin permeability and the effects of tooth reduction. Two different methods of tooth reduction were used. In group 1, tooth reduction was nonuniform but was done in a manner similar to conventional crown preparations. Maximum, total crown permeability was measured using a pressurized fluid filtration technique after removing the smear layer. Regional reductions in permeability were accomplished by creating smear layers on mesial, distal, buccal, lingual, and occlusal surfaces sequentially. Between each step, changes in dentin permeability were measured. In group 2, tooth reductions were uniform and regional permeability was reduced by localized application of potassium oxalate. Both methods demonstrated increased permeability of dentin as the prepared surfaces approached the pulp chamber. Generally, the mesial surfaces were more permeable than the distal surfaces. The occlusal and lingual surfaces were the least permeable regions.

Adult↗

Permeability characteristics of deoxygenated sickle cells.

This study investigated the effect of acute deoxygenation on membrane permeability characteristics of sickle cells. Measured fluxes of Na+ and K+ in ouabain-inhibited cells, of chloride and sulfate exchange in 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS)-inhibited and untreated cells, and of erythritol, mannitol, and arabinose in cytochalasin B-inhibited cells indicated that a deoxygenation-induced permeability change occurred in sickle cells only for cations and chloride. Monovalent cation permeabilities increased five-fold, and chloride influx into DIDS treated cells was enhanced nearly threefold on sickle cell deoxygenation. In contrast, no detectable increase in permeability to the other solutes was found. To gain perspective on these findings, similar measurements were performed in normal cells treated with diamide, an agent shown by others to induce a coupled increase in membrane permeability and phospholipid translocation, reminiscent of deoxygenation-induced changes in sickle cells. Although the increase in cation permeability was no greater than that in sickled cells, treatment with 2 mmol/L diamide also produced a twofold increase in the first order rate constants for sulfate exchange and mannitol efflux, indicating a relatively nonselective permeability increase that permitted flux of larger solutes than in the case of deoxygenated sickle cells. These results suggest that the deoxygenation of sickle cells induces a permeability increase that is relatively insensitive to charge, but is restrictive with respect to solute size.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

The effect of platelet-activating factor (PAF), histamine, and ethanol on vascular permeability of the guinea pig conjunctiva.

Increased vascular permeability, one of the characteristic features of immediate hypersensitivity (Type I), is mediated through a variety of compounds, including histamine and platelet-activating factor (PAF), a phospholipid inflammatory mediator. The effects on vascular permeability of histamine, PAF, and ethanol, the solvent for PAF, were compared in the guinea pig conjunctiva. Permeability at 30 min was investigated by evaluation of conjunctival edema and Evans blue extravasation (clinically estimated and colorimetrically measured). Doses of PAF from 1 to 10 nmol produced an increase in vascular permeability, with a peak effect at 10 nmol. Ethanol had no effect on vascular permeability below 40 X 10(3) nmol; above this concentration, however, permeability increased, reaching a maximum at 175 X 10(3) nmol. At low doses of PAF and ethanol, the effects were additive, whereas at 20-80 nmol of PAF with high concentrations of ethanol there was no additive effect of PAF, producing a decrease in the net effect of PAF. Histamine increased vascular permeability, with a minimum effect at 10 nmol and a maximum effect at 450 nmol. The slopes of the dose-response curves for all three compounds were linear and parallel, with statistically different potencies. The potencies for each compound were identical by all three methods of evaluation. Therefore, we conclude that PAF is a potential mediator in hypersensitivity reaction in the guinea pig conjunctiva, and that its effect is similar to but much more potent than that of histamine or ethanol. Since ethanol alone has a significant effect on vascular permeability, studies on PAF effects using control solutions without ethanol may be difficult to interpret.

Animals↗

[A study on the vascular permeability of brain tumors using dynamic CT].

The vascular permeability of 50 brain tumors of various kinds was examined by means of dynamic CT. The degree of the vascular permeability within the tumor was evaluated according to the theoretical basis that the regression of the time-density curve after the peak to the base line became less in accord with the increase in vascular permeability. The time-density curves obtained from dynamic CT were classified into the following four types. Type 1; This type shows a similar pattern to normal brain tissue and is thought to reveal the normal vascular permeability. Type 2; this type shows intermediate pattern between type 1 and type 3. And the vascular permeability is thought to have been moderately increased. Type 3; This type shows the flattening or gradual increase in the time-density curve after forming the peak. The vascular permeability is thought to have increased markedly. Type 4; The peak of the time-density curve is lower than that of the white matter. This type of tumor is regarded to be least vascularized. All tumors except for gliomas and AVMs showed type 2 or 3 and their vascular permeability was thought to be increased. Most of the gliomas showed type 2 or 3, although some gliomas showed type 1 even in the lesion with positive contrast enhancement. In the lesions of such cases, it was thought that the vascular permeability was not affected significantly, so that blood brain barrier modification therapy by intraarterial mannitol infusion may be quite effective. All AVMs showed type 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epithelial permeability produced by phagocytosing neutrophils in vitro.

Neutrophils are thought to increase alveolar permeability in many types of lung injury. To investigate the contribution of neutrophils to the development of permeability pulmonary edema, we have developed an in vitro cell culture system for studying alveolar epithelial permeability. Rat alveolar type II cells, cultured for 6 to 12 days on collagen-coated Millipore filters, form a morphologically and pharmacologically polarized epithelium. The filters are mounted between 2 lucite chambers, and electrical resistance (permeability to ions) and spontaneous potential difference across the monolayer are measured continually or at frequent intervals. When neutrophils and the phagocytosable particle, opsonized zymosan (but not neutrophils or opsonized zymosan alone), were added to the apical side, the potential difference and transepithelial resistance fell dramatically after 20 min, which indicates an increase in epithelial permeability. The increase in epithelial permeability was inhibited by serum alpha-1-protease inhibitor (250 micrograms/ml), methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone (0.02 mM) (an elastase inhibitor), catalase (2,500 units/ml), and superoxide dismutase (330 units/ml). In experiments with a lower concentration of phagocytosing neutrophils, a slower rate of decrease in resistance occurred, and in 3 of 13 studies, there was a definite recovery of the resistance to initial values. This study demonstrated that phagocytosing but not resting neutrophils increase the permeability of the epithelial monolayers to ions and suggests that the increased permeability in this system is mediated in part by both neutral protease(s) and oxygen radicals.

Animals↗

A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines.

We have previously reported that rodent tumor cell lines secrete a potent vascular permeability factor with a molecular weight of 34,000-42,000 (Senger et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (Wash. DC), 219: 983-985, 1983). This tumor-secreted vascular permeability factor (VPF) causes a rapid and completely reversible increase in microvascular permeability in the species (guinea pig or rat) from which the tumors were derived without causing mast cell degranulation or endothelial cell damage or exciting an inflammatory cell infiltrate. This VPF may be responsible, at least in part, for the increased permeability which is commonly displayed by solid and ascites tumor vessels. We have now examined 7 human tumor cell lines and have determined that 5 of them also secrete this same VPF. Antibody raised to guinea pig line 10 VPF neutralized more than 90% of the vascular permeability-increasing activity secreted by these 5 human tumor lines. Furthermore, VPFs from both guinea pig and human tumor sources bound to and were eluted similarly from immobilized heparin and comigrated identically on sodium dodecyl sulfate-polyacrylamide gels. Finally, 2 tumorigenic (in nude mice) human cell lines were found to secrete at least 14-fold more VPF than their directly matched, nontumorigenic counterparts, suggesting that elevated expression of this permeability factor may correlate with neoplastic transformation. These data suggest that a broad spectrum of tumor cells from several species, including humans, secretes a highly conserved molecule that enhances local vascular permeability and that this function may be important for tumor growth.

Animals↗

Estimation of the permeability of the blood-retinal barrier in normal individuals.

The fluorescein kinetics in the vitreous was simulated with a computer to consider several factors such as permeability of the blood-retinal barrier, outward active transport, plasma fluorescein dynamics, diffusion of fluorescein in the vitreous, and fluorescein leakage from the blood-aqueous barrier. Kinetic vitreous fluorophotometry was performed in normal individuals to estimate the inward and outward permeability of the blood-retinal barrier based on the theory of the simulation model. The results of the simulation studies suggest that the fluorescein concentration in the posterior vitreous after intravenous administration is dependent mainly on the inward permeability and on the plasma concentration and that the outward permeability has little influence on the fluorescein kinetics at the early phase. In the pharmacokinetic analysis of the results of kinetic vitreous fluorophotometry, we obtained average values of 1.8 X 10(-5) cm/min and 5.6 X 10(-4) cm/min for the inward permeability and outward permeability coefficients, respectively. The diffusion coefficient of fluorescein in the vitreous was estimated at 7.9 X 10(-4) cm2/min on the average. The outward permeability of the blood-retinal barrier is approximately 31 times the inward permeability. This suggests that a facilitated process that transports fluorescein outward from the vitreous cavity exists in the blood-retinal barrier of human eyes.

Adolescent↗

Human scleral permeability. Effects of age, cryotherapy, transscleral diode laser, and surgical thinning.

PURPOSE: To determine the in vitro permeability of human sclera to compounds varying in molecular weight. To evaluate the effects of age, cryotherapy, transscleral diode laser, and surgical thinning on scleral permeability. METHODS: Scleral tissue from 97 human eye bank eyes was tested individually in a two-chamber Ussing apparatus with the following hydrophilic radiolabeled compounds on one side of the chamber: 5-fluorouracil, sucrose, dexamethasone, methotrexate, inulin, and three separate dextran polymers (MWt = 10,000, 40,000, and 70,000). Scleral hydration levels were obtained on 20 more scleral specimens. Additional groups of scleral specimens were treated with either a cryotherapy probe, a transscleral diode laser retinopexy probe, or partial thickness lamellar dissection, and specimens were mounted in the Ussing chambers for testing. Scleral tissue was digested to measure the amount of radioactivity present. Scleral sections were examined with electron microscopy. RESULTS: Scleral hydration was maintained during the perfusion. The mean scleral permeability (cm/second x 10(-6) +/- SD) was established for each of the above compounds. Age, cryotherapy, or diode laser treatment did not alter permeability or ultrastructure of the sclera. Surgical thinning significantly increased the scleral permeability to dexamethasone (P = 0.011) and methotrexate (P = 0.037). CONCLUSION: This study establishes baseline human scleral permeability to a series of hydrophilic compounds with various molecular weights. Age, cryotherapy, and diode laser treatment do not alter the permeability or ultrastructure of the sclera, whereas surgical thinning significantly increases permeability.

Adolescent↗

Effect of superoxide exposure on albumin permeability of isolated rat glomeruli.

Reactive oxygen radicals generated by mesangial cells or by resident or infiltrating macrophages may contribute to glomerular injury in glomerulonephritis. To determine whether superoxide anions have an effect on the glomerular barrier to macromolecules, we studied the responses of isolated glomeruli after exposure to superoxide generated by xanthine and xanthine oxidase or by activated macrophages. Glomerular volumetric responses to oncotic gradients of bovine serum albumin or an impermeant neutral dextran (mol wt 252 kd0 were used to calculate the albumin reflection coefficient (sigma albumin) and convectional permeability to albumin (1-sigma albumin) of control and superoxide-treated glomeruli. Albumin permeability of control glomeruli was not different from 0 (0.02 +/- 0.01, N = 50). After 10 minutes of exposure of glomeruli to superoxide generated by xanthine oxidase, albumin permeability was increased to 0.06 +/- 0.01 (N = 50). Albumin permeability did not increase further after incubations with xanthine and xanthine oxidase for up to 60 minutes. The increase in albumin permeability was prevented by superoxide dismutase (-0.02 +/- 0.01, N = 48) but was not affected by catalase or by indomethacin pretreatment. Coincubation of glomeruli with activated macrophages also increased albumin permeability to a maximum of 0.80 +/- 0.05 (N = 17). Albumin permeability was not increased by incubation of glomeruli with phorbol myristate acetate alone or with macrophages in the absence of phorbol myristate acetate. The effect of activated macrophages on albumin permeability, like that of superoxide generated chemically, was prevented by superoxide dismutase but not by catalase or indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

[Relationship between intestinal permeability and antibodies against food antigens in IgA nephropathy].

Elevated antibody titers to food antigens and increased intestinal permeability in IgA nephropathy (IgA NP) suggest that these factors may be interdependent and play a role in the pathogenesis of the disease. In 1989 IgA and IgG antibodies against eight common food antigens were examined in the sera of 35 IgA NP patients and 12 controls using the ELISA method. Intestinal permeability was determined in 29 IgA NP patients and 20 controls using the 51Cr-EDTA test. Both examinations were carried out in 17 patients. Twenty-one patients allowed the intestinal permeability examinations to be repeated five years later. Compared with controls, significantly elevated IgA antibody titers against gliadin, soy, HAV (salt extracted antigens of oat flour) and ovalbumin were found. Intestinal permeability was significantly higher in IgA NP patients both in 1989 (3.86% +/- 0.29 vs. control, 2.72% +/- 0.23; p < 0.005) and in 1994 (4.57% +/- 0.63; p < 0.02) than in controls. A strong correlation was observed between the intestinal permeability and the IgA type of antibody titers against soy (p < 0.01; r = 0.72) and HAV (p < 0.02; r = 0.57). In patients without azotemia (serum creatinine > 150 mumol/l; n = 22) the decrease in creatinine clearance was significant only in the cases of increased intestinal permeability. On the basis of these data we assume that there is a connection between intestinal permeability and the production of IgA type antibody against food antigens in least a proportion of patients with IgA NP, and as a results of the lasting increase in intestinal permeability the production and the mesangial deposition of IgA immunocomplexes also increase.

Antibodies↗

A quantitative assay for experimental allergic encephalomyelitis in the rat based on permeability of spinal cords to 125I-human gamma-globulin.

We have developed a quantitative assay for experimental allergic encephalomyelitis (EAE) in the rat based on permeability of the spinal cord to 125I-human gamma-globulin (HGG). This assay is highly reproducible and eliminates many of the drawbacks of assaying for EAE on the basis of clinical and/or histologic criteria. Using the assay, we have shown a direct correlation between onset of histologic changes in the spinal cord and onset of permeability changes in the spinal cord. No rat without histologic lesions manifest permeability alterations, and all rats with histologic lesions did manifest increased permeability to 125I-HGG. Furthermore, strains of rats susceptible to EAE demonstrated permeability changes, whereas resistant rats did not. In addition, we demonstrated by permeability and histologic criteria that guinea pig myelin basic protein emulsified with incomplete Freund's adjuvant is encephalitogenic in the Lewis rat. We also demonstrated that recipients of passive transfer of sensitized cells develop permeability changes along with histologic lesions. We conclude that measuring permeability to 125I-HGG in the spinal cords of rats is a valid assay for EAE, and its improves upon current indices of EAE in that it is readily quantifiable.

Animals↗

[Airway hyperresponsiveness and airway mucosal permeability].

The relationship between airway mucosal permeability and airway hyperresponsiveness was examined with tachykinins, their selective antagonists, and superoxide dismutase in male Hartley guinea pigs. In animals with ozone-induced airway inflammation, airway hyperresponsiveness and mucosal permeability increased concurrently but there was a time lag before the increase in airway vascular permeability. To study the role of tachykinins in the increases in mucosal permeability and in hyperresponsiveness, we used a neurokinin-receptor antagonist, CP-96345, and a neurokinin-2 receptor antagonist, SR-48968. CP-96345 had no significant effect, but SR-48968 reduced the increase in airway mucosal permeability; their effects on airway hyperresponsiveness were the opposite of their effects on airway permeability. Tachykinins themselves, both substance P and neurokinin A, significantly increased airway mucosal permeability. Superoxide dismutase, a scavenger enzyme of superoxide, reduced the ozone-induced airway hyperresponsiveness. These data suggest that the factors causing airway hyperresponsiveness differ from those that influence mucosal permeability, but it is possible that these pathophysiologic conditions are caused by the same substances or processes.

Animals↗

Local hemodynamics, permeability, and oxygen metabolism during acute inflammation of innervated or denervated isolated equine joints.

OBJECTIVES: To determine oxygen metabolism, permeability, and blood flow in isolated joints in response to interleukin 1beta (IL-1beta) and contribution of innervation. SAMPLE POPULATION: One metacarpophalangeal (MCP) joint of 24 adult horses. PROCEDURE: The MCP joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated preparation. Isolated joints were assigned to the following 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular injection of IL-1beta. Circuit arterial and venous pressures, flows, and blood gas tensions, synovial fluid production, and intra-articular pressure were measured. Total vascular resistance; oxygen delivery, consumption, and extraction ratio (ER); and permeability surface area product were calculated. Synovial membrane blood flow was determined at 0, 60, and 330 minutes. Synovial membrane wet-to-dry ratio was obtained, and permeability to macromolecules was determined by intra-articular injection of Evans blue albumin and fluorescein isothiocyanate-conjugated dextran. RESULTS: Oxygen delivery and synovial membrane blood flow progressively increased but were not different among groups. Oxygen consumption and ER significantly increased in inflamed joints, as did intraarticular pressure and synovial fluid production. Inflamed joints had greater wet-to-dry ratio. Albumin permeability significantly increased in the villous synovial membrane of the inflamed groups, and dextran permeability was increased in the innervated groups, with a trend toward increased permeability in inflamed groups. CONCLUSION: Inflammation significantly increased oxygen demand, which was initially met by increased ER. Permeability to small molecules was increased with inflammation; innervation increased permeability to large molecules. Use of an isolated joint model enabled documentation of the physiologic responses of the joint to acute inflammation.

Albumins↗

Histamine does not mediate mucosal permeability changes after subclinical intestinal ischemia-reperfusion injury.

UNLABELLED: Subclinical intestinal ischemia-reperfusion injury (IRI) increases mucosal permeability, and may be an important mechanism in the etiology of necrotizing enterocolitis. The current study was designed to assess the role of histamine in mediating this phenomenon. Six-week-old rats underwent 10-minute superior mesenteric artery occlusion (SMAO) or sham operation, and ileal mucosal permeability to 51Cr EDTA was measured 30 minutes after reperfusion. Rats were pretreated with intravenous saline, mepyramine (6 mg/kg), or ranitidine (5 mg/kg). SMAO resulted in a significant increase in permeability compared to sham, which was not attenuated by either of the histamine antagonists. In a second experiment, mucosal permeability to 51Cr EDTA was measured in 6-week-old rats during aortic infusion of saline or histamine (0.5 mg/kg/min). There was no significant increase in permeability as a result of histamine infusion. In a third experiment, 6-week-old and 10-day-old rats underwent sham or 10-minute SMAO, and both portal vein and ileal tissue histamine levels were measured 30 minutes after reperfusion. There was no significant difference between sham and SMAO with respect to portal vein histamine or tissue histamine at either age. IN CONCLUSION: (1) increased permeability was not blocked by either H1 or H2 blockers; (2) histamine infusion did not increase permeability; and (3) SMAO did not increase portal vein or tissue histamine levels. These data suggest that histamine does not play a role in mediating the increase in permeability after subclinical IRI in this model.

Animals↗

Probable involvement of serotonin in the increased permeability of the blood-brain barrier by forced swimming. An experimental study using Evans blue and 131I-sodium tracers in the rat.

The possibility that endogenous serotonin (5-hydroxytryptamine, 5-HT) participates in alteration of the blood-brain barrier (BBB) following short-term forced swimming (FS) exercise was examined in a rat model. Subjection of conscious young (age 8-9 weeks, 80-90 g) animals to continuous FS (at a water temperature of 30 +/- 1 degrees C) for 30 min, increased the permeability of the BBB to Evans blue albumin (EBA) and 131I-sodium in six and nine brain regions, respectively. The EBA staining was noted in posterior cingulate cortex, parietal, occipital cortices, cerebellar vermis, medial lateral cerebellar cortices and dorsal surface of hippocampus. In addition to these brain regions, the BBB permeability to 131I-sodium was further extended to caudate nucleus, thalamus and hypothalamus. This effect of FS on the BBB permeability was absent in adult (age 24-30 weeks, 300-400 g) animals. Measurement of 5-HT showed a profound increase of plasma and brain in young rats by 180% and 250%, respectively, from the control group. Adult animals showed only a minor increase in brain and plasma 5-HT levels. In young animals, pretreatment with p-CPA (a 5-HT synthesis inhibitor) and indomethacin (a prostaglandin synthesis inhibitor) prevented the FS induced increase in BBB permeability and 5-HT levels. Destruction of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the breakdown of the BBB and attenuated the brain 5-HT level without affecting the plasma 5-HT. Cyproheptadine, ketanserin (5-HT2 receptor antagonists) and vinblastine (a vesicular transport inhibitor) prevented the increased permeability of the BBB alone. The plasma and brain 5-HT continued to remain high. These observations suggest that (i) 5-HT plays an important role in the breakdown of BBB permeability in FS, (ii) this effect of 5-HT on BBB permeability is mediated by 5-HT2 receptors, and (iii) FS induced increase in BBB permeability is age dependent.

5,7-Dihydroxytryptamine↗

Treatment of persistent corneal epithelial defect with extended wear of a fluid-ventilated gas-permeable scleral contact lens.

PURPOSE: To report treatment of persistent corneal epithelial defects unresponsive to other therapies by extended wear of a fluid-ventilated gas-permeable scleral contact lens. METHODS: In this retrospective study, 14 eyes of 13 consecutive patients referred for the treatment of persistent corneal epithelial defects that failed to heal with conventional therapies or developed epithelial defects after penetrating keratoplasty for persistent corneal epithelial defects were fitted with an extended-wear gas-permeable scleral lens. These included seven eyes of six patients with Stevens-Johnson syndrome and seven eyes of seven patients who did not have Stevens-Johnson syndrome. Twelve eyes had undergone recent penetrating keratoplasty. All 14 eyes were fitted with a gas-permeable scleral contact lens designed to avoid the intrusion of air bubbles under its optic. An antibiotic and corticosteroid were added to the lens fluid reservoir or instilled before each lens insertion in 12 of 14 eyes. The lenses were worn continuously except for brief periods of removal for purposes of cleaning, replacement of the lens fluid reservoir, and examination and photography of the cornea. RESULTS: Five of the seven persistent corneal epithelial defects associated with Stevens-Johnson syndrome healed. The persistent corneal epithelial defects of four of these eyes re-epithelialized within 7 days, and a fifth healed in 27 days of gas-permeable scleral lens extended wear. A sixth persistent corneal epithelial defect that failed to heal initially re-epithelialized after a subsequent penetrating keratoplasty and gas-permeable scleral lens extended wear. The seventh eye healed after 3 days of gas-permeable scleral lens extended wear, but the persistent corneal epithelial defect subsequently recurred. Three of seven non-Stevens-Johnson syndrome persistent corneal epithelial defects re-epithelialized within 36 hours, 6 days, and 36 days, respectively. Of the six (six of 14) persistent corneal epithelial defects that failed to heal with a gas-permeable scleral lens extended wear, one subsequently healed after multiple amniotic membrane grafts. Microbial keratitis occurred in four eyes (four of 14) and graft failure in one eye, all of which required repeat penetrating keratoplasty. CONCLUSION: Extended wear of an appropriately designed gas-permeable scleral contact lens was effective in promoting the healing of persistent corneal epithelial defects in some eyes that failed to heal after other therapeutic measures. Re-epithelialization appears to be aided by a combination of oxygenation, moisture, and protection of the fragile epithelium afforded by the scleral lens. However, microbial keratitis represents a significant risk.

Adolescent↗