Comparison of complications after Ahmed versus Baerveldt implant in glaucoma patients: one year follow-up

AIM: To compare surgical results of the Ahmed and Baerveldt implant procedures in glaucoma patients at 1y follow-up at Jakarta Eye Center (JEC) Eye Hospitals. METHODS: This cohort retrospective study was conducted on glaucoma patients aged ≥18y who had undergone Ahmed and Baerveldt implant surgery. Intraocular pressure (IOP), visual acuity, glaucoma medication, success rate, early and late postoperative complications, and the number of resurgeries were analyzed. RESULTS: A total of 351 eyes in the Ahmed group and 94 eyes in the Baerveldt group were included in this study. At 1y follow-up, the mean IOP was found to be significantly lower in the Baerveldt group (13±4.47 mm Hg) compared to the Ahmed group (15.02±5.73 mm Hg; P=0.025). Glaucoma medication was required in both the Ahmed and Baerveldt groups (58.92% vs 71.67%). Comparable success rate was found in both groups. The Ahmed group revealed a complete and qualified success of 86.82%, and failure of 13.17%. Similarly, the Baerveldt group showed complete and qualified success in 87.75% and failure in 12.25% cases. In the Ahmed group, 11.97% early complications, 26.06% late complications and 9.97% resurgeries were observed. In comparison, in the Baerveldt group, 23.40% early complications, 30.95% late complications and 11.70% resurgeries were observed. CONCLUSION: Both groups of glaucoma implants show significant IOP reduction, however, the Baerveldt implant group demonstrates greater IOP reduction with more failure rates and complications than the Ahmed implant group.     

Anticomplementary activity of cornea, vitreous and chorioretina in rabbits.

We wished to determine if inhibitors of the complement system are present in different rabbit ocular tissues. Soluble extracts of cornea, vitreous humor and chorioretina in different dilutions were incubated with normal human serum (as source of complement). The ability of the latter to lyse sheep erythrocytes sensitized with antisheep rabbit hemolysin was assessed. The cornea did not show any inhibition of complement. The vitreous humor exhibited very low inhibitory activity. The extracts of the uveo-retinal tissue contained heat-labile and heat-stable factors capable of cleaving C3 and factor B.     

Role of lymphocyte and antibody in the pathogenesis of immune-mediated herpetic uveitis

We investigated the role of various immune components in the pathogenesis of immune-mediated experimental herpetic uveitis. Inbred III/J strain of rabbits were sensitized with an intravitreal injection of 10(3) PFU of type 1 herpes simplex virus (HSV), and sensitized cervical lymph node (LN) cells were obtained on postinfection day 12. Intravitreal injection to the normal III/J rabbit eye of HSV antigen with either sensitized LN cells or anti-HSV serum failed to induce uveitis, whereas intravitreal injection of HSV-antigen with both sensitized LN cells and anti-HSV serum produced severe uveitis within six hours. The combination of sensitized LN cells, HSV-antigen and normal rabbit serum, or that of normal LN cells, HSV antigen and anti-HSV serum, did not induce uveitis. Further studies using B lymphocyte and T lymphocyte fractions from sensitized LN showed that only the combination of sensitized T lymphocytes, HSV antigen and anti-HSV serum regularly produced uveitis following intravitreal injection. These results indicate that the interaction of HSV antigen, sensitized T lymphocytes and anti-HSV antibody may play a role in the pathogenesis of immune-mediated herpetic uveitis.     

Intraocular penetration kinetics of prednisolone after subconjunctival injection in rabbits

Prednisolone concentrations in cornea, aqueous humor, and vitreous humor and the residual amount in conjunctival tissue were assayed by high-performance liquid chromatography during a 14-hour period after subconjunctival injection of prednisolone sodium succinate in rabbits. Prednisolone was concentrated in the corneal epithelium and reached a peak within 5 min, whereas the peak level of prednisolone in stroma-endothelium was achieved 1 h after the injection. There was an apparent linear binding of prednisolone with the ocular tissue homogenates and fluids except for the vitreous humor. However, the protein binding of prednisolone with vitreous humor showed marked concentration dependency. A pharmacokinetic model involving a rapid conversion to prednisolone from its ester prodrug, first-order transfer to various tissues, and first-order elimination of unbound prednisolone from vitreous humor succeeded in predicting the observed concentration-time profiles of prednisolone in various ocular tissues and fluids after subconjunctival injection at three different doses: 0.1, 1.0, and 10.0 mg/kg. The present model predicted that absorption into precorneal area and epithelium and direct penetration into aqueous humor and vitreous humor are 1.7, 0.1, and 0.2% of the applied dose, respectively, and that almost the entire dose (98%) is absorbed into the systemic circulation, with a half-life of 38 min.     

Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

AIM:To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid) (PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.METHODS:Bevacizumab was encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil (S/O/hO) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.RESULTS:The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes (P<0.05). The AUC0-t of the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly. The immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA) in rabbit eye tissues was still observed up to 42d. It was longer than that of the soluble form.CONCLUSION: The result of this study shows the beneficial effects of PLGA in prolonging the residency of bevacizumab in the vitreous. And the drug delivery system may have potential as a treatment modality for related disease.     

The influence of cyclosporin A on proteininduced uveitis in the rabbit

Until now immunosuppressive drugs have mainly been used to treat ocular diseases considered to have an autoimmune pathogenesis. The authors investigated whether cyclosporin A (CsA) could also prevent intraocular inflammation mediated by a foreign antigen. To this purpose, uveitis was induced by injection of human serum albumin (HSA) into the vitreous of rabbits. Subcutaneous injection of CsA prevented the induction of uveitis. Treatment of CsA had to be started at the time of intravitreal antigen injection and did not suppress the reaction when started at the onset of uveitis. Suppression of uveitis correlated with an inhibition of the antibody response against the injected HSA. Animals in which uveitis was suppressed by CsA did not develop a recurrent uveitis after intravenous challenge with the antigen, but did develop a primary inflammatory response after a repeated injection of HSA into the vitreous. The most likely interpretation of the findings presented in this paper are as follows. CsA blocks T helper cells through an inhibition of IL-2 gene activation. This in turn blocks release of other T helper cell cytokines which are essential for the activation of B lymphocytes into antibody producing plasma cells. These observations thus show that CsA can suppress both cell-mediated as well as antibody-mediated models of uveitis.     

Ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade

Purpose. We characterized the ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade. Methods. A total of 18 pigmented rabbits underwent vitrectomy and silicone oil tamponade before an intra-silicone oil injection of 1.25 mg bevacizumab. At post-injection days 1, 7, 14, 28, 42, and 56, 3 rabbits were sacrificed and enucleated, and bevacizumab concentrations were measured in various ocular tissues and plasma. Results. The bevacizumab peak concentration was reached at day 14 in the aqueous humor (4030.70 ng/mL), retina (42,171.7 ng/g), and choroid (56,243.33 ng/g). In the iris/ciliary body and plasma, the peak concentration was reached at day 7 with 52,648.30 ng/g and 197.70 ng/mL, respectively. The choroid had the maximum exposure to bevacizumab with an area under the curve calculated from time zero to the last observed time (AUC(last)) of 1,151,633.40 ng/day/g and the aqueous humor had the minimum exposure (AUC(last) = 74,611.28 ng/day/g) among the ocular tissues, while the drug exposure to the plasma was the smallest of all tissues studied (AUC(last) = 3795.17 ng/day/g). The terminal half-lives and the mean residence time of bevacizumab in the ocular tissues ranged from 3-5 and 10-13 days, respectively. Conclusions. The peak concentration of bevacizumab in various ocular tissues and plasma was delayed and lower than that found in normal rabbit eyes; however, the terminal half-lives were similar to those found in the eyes with native vitreous following an intravitreal injection. Oil may have impacted the distribution of bevacizumab and led to an altered profile of drug level in the ocular tissues.     

Experimental uveitis in isolated humoral and cellular immunity

Summary Passive transfer of homologous immune serum in rabbits followed by intravitreous injection with the corresponding antigen resulted in an uveal inflammation which resembled the Arthus-type reaction. Clinically and histologically, the reaction was maximal 24 h after antigen injection. The histologically observed cell infiltration consisted predominantly of polymorphonuclear leukocytes.Passive transfer of sensitized homologous thymocytes followed by intravitreous injection with the corresponding antigen resulted in an uveal inflammation which resembled the delayed-type hypersensitivity reaction. Tissue infiltration of polymorphonuclear cells as well as mononuclear cells occurred predominantly during the first day following antigen injection. An exudate containing almost exclusively eosinophils was present in the aqueous humor and/or vitreous body of most of these rabbits. During the second day an increase in the ratio mononuclear cells/polymorphonuclear cells could be observed.     

Endotoxin-induced uveitis (EIU) in the rat: A study of inflammatory and immunological mechanisms

Endotoxin-induced uveitis (EIU) can be produced by systemic injection of endotoxin (ET). It is not clear yet why exclusive ocular involvement occurs in this model. To clarify this question and to establish the sequence of inflammatory events, EIU was induced in Lewis rats by footpad injection of Salmonella ET. Ocular inflammatory response (anterior chamber cells and proteins), aqueous inflammation mediators (thromboxane B₂, prostaglandin E₂, leukotriene B₄ and substance P) and MHC class 2 (Ia) antigen expression in the ciliary body were monitored for 72 hours. Thromboxane B₂ was detected early in the aqueous humor, peaking already 1 hour after ET injection. Prostaglandin E₂ & leukotriene B₄ peaks and a second peak of thromboxane B₂ were recorded 18 hours after ET-injection, at the time of maximal ocular inflammation. MHC-class 2 expression was first detected in the ciliary body stroma at the vascular level 6 hours after ET injection and was massively expressed in the ciliary body epithelium at 18 and 72 hours. It is hypothetized that ciliary body endothelium is particularly sensitive to the effect of ET and is the site of thrombocyte adherence. Vascular damage leads in succession to cellular infiltration, release of inflammation mediators and disruption of blood-ocular barrier. MHC-class 2 expression is a secondary phenomenon and is probably at the origin of additional tissue damage from immune effector mechanisms.     

Induction of genes into the rabbit eye by iontophoresis

PURPOSE: After inducing 6-carboxyfluorescein (6-FAM)-labeled phosphorothioate oligonucleotides (S-ODNs) noninvasively into albino rabbit eyes by iontophoresis, we assessed the transfer of S-ODNs into the ocular tissues, their stability, and the possible presence of injury to the ocular tissues. METHODS: The iontophoresis group consisted of 12 eyes of 6 rabbits and the control group consisted of 4 eyes of 2 rabbits given eye drops containing S-ODNs. Aqueous humor and vitreous humor were collected after iontophoresis, subjected to electrophoresis with a fluorescent DNA sequencer and analyzed by the Gene Scan program. Frozen sections at 10 microns were prepared for observations under a fluorescent microscope. A plasmid 4.7 kbp in size that expresses green fluorescent protein (GFP) was induced into 18 eyes of 9 rabbits by the same procedure. RESULTS: In the iontophoresis group, S-ODNs were detected in the anterior chamber 5 minutes after electrophoresis and in the vitreous 10 minutes after. These S-ODNs maintained the same length as at the initial synthesis. S-ODNs could also be detected in the posterior retina 20 minutes after electrophoresis. No evidence of degeneration or inflammation due to the above procedure was found in the ocular tissues. Fluorescence showing GFP gene expressions were found in the cornea, the anterior chamber angle, and the ciliary subepithelial tissues. CONCLUSIONS: These findings show that iontophoresis is an effective method to induce gene into rabbit eyes.     

Intravitreal delivery of oligonucleotides by sterically stabilized liposomes.

PURPOSE: The efficacy of sterically stabilized liposomes for delivering a model phosphodiester oligonucleotide intravitreally was investigated in the rabbit. METHODS: Ocular distribution and clearance from the vitreous humor of a model 16-mer oligothymidylate (pdT16) were evaluated in the rabbit by radioactivity measurements after intravitreal injection of either a solution or liposomes containing the [33P]pdT16 oligonucleotide. The integrity of pdT16 was investigated using a competitive hybridization assay. RESULTS: The residual concentration of the [33P]pdT16 oligonucleotide within the ocular tissues was significantly increased after intravitreal administration of the liposomal suspension compared with a simple solution. Administration of liposome-encapsulated pdT16 oligonucleotide resulted in sustained release into the vitreous and the retina-choroid compared with release from the solution and in a reduced distribution to nontarget tissues (sclera, lens). In addition, liposomes protected the phosphodiester oligonucleotide against degradation. This was not observed after administration of the free oligonucleotide. CONCLUSIONS: The intravitreal injection of a phosphodiester oligonucleotide encapsulated within liposomes is a new way of delivering intact oligonucleotide to the eye in a controlled manner. This offers interesting prospects for the treatment of retinal diseases.     

Intraocular penetration of gentamicin after subconjunctibal and retrobulbar injection .

We compared the ocular penetration of labeled with radioactive carbon gentamicin in squirrel monkeys after subconjunctival and retrobulbar administration. In both normal and infected (Staphylococcus aureus endophthalmitis) eyes, high concentrations of drug were achieved in the sclera and choroid-retina by both routes, while corneal levels were markedly higher after subconjunctival injection than after retrobulbar injection. Regional variations in concentration were evident in these tissues; the highest levels were clustered about the site of injection. Aqueous humor concentrations were lowest in the group with normal eyes treated by the retrobulbar route; vitreous humor levels were extremely low in normal eyes injected subconjunctivally. These data differ from those in rabbits, especially with regard to penetration of the vitreous humor of normal eyes. Interspecies differences were less marked in inflamed eyes. The two species were similar in demonstrating maximum access to the cornea and aqueous humor with subconjunctival injection, and equivalence of the two routes in penetrating the vitreous humor of the inflamed eyes.     

Induction of gene into the rabbit eye by iontophoresis: preliminary report

PURPOSE: To assess the transfer of 6-carboxyfluorescein (6-FAM)-labeled phosphorothioate oligonucleotides(S-ODNs) into the ocular tissues, their stability, and possibility of injury to the ocular tissues. METHODS: The S-ODNs(2 mL/eye)were transduced noninvasively into albino rabbit eyes.The iontophoresis group consisted of 6 rabbits (12 eyes); the control group consisted of 2 rabbits (4 eyes) given eye drops containing S-ODNs. Aqueous humor and vitreous humor were collected after iontophoresis, subjected to electrophoresis with a fluorescence DNA sequencer and analyzed by the Gene Scan program. Frozen sections, 10-microm thick, were prepared for observation under a fluorescence microscope. A plasmid 4.7 kbp in size that expresses green fluorescent protein (GFP) was induced into the 18 eyes of 9 rabbits by the same procedure. RESULTS: In the iontophoresis group, S-ODNs were detected in the anterior chamber 5 minutes after electrophoresis began and in the vitreous after 10 minutes. These S-ODNs maintained the same length as at the initial synthesis. The S-ODNs could also be detected in the posterior retina 20 minutes after electrophoresis. No evidence of degeneration or inflammation due to the above procedure was found in the ocular tissues. Fluorescence showing GFP gene expression was found in the cornea, the anterior chamber angle, and the ciliary subepithelial tissues. CONCLUSIONS: These findings show that iontophoresis is an effective method to induce genes into the rabbit eye.     

两种不同注射方法眼局部注射鼠神经生长因子后兔眼内药物分布

目的 观察兔玻璃体腔注射与球周注射~(125)I-神经生长因子(NGF)后眼部各组织药物含量分布.方法 45只家兔分别于左眼玻璃体腔(A组)和右眼球周(B组)注射~(125)I-NGF 30 μg/100μl.于注药后15、30 min,1、3、6、8、12、24、48 h取眼房水、玻璃体等眼内容物,角膜、巩膜等眼球外壁组织,虹膜睫状体、视网膜、脉络膜等眼球内壁组织进行γ-计数,计算~(125)I-NGF的含量.结果 A组药物在眼内容物及眼球内壁各组织弥散较快,玻璃体内含量呈梯度下降,其它眼内组织含量呈正态曲线变化;房水、虹膜睫状体、视网膜、脉络膜达峰值时间均为给药后3 h,巩膜、角膜分别为6、8 h;B组眼内各组织药物含量呈正态曲线变化,药物达眼内峰值时间较慢,除房水在给药后3 h达峰值,其他组织均在6 h达峰值;A组各组织~(125)I-NGF峰值含量也明显高于B组;A组除玻璃体直接注射导致高药物含量外,视网膜药物含量最高.结论 玻璃体腔注射~(125)I-NGF较球周注射更能在眼内各组织达到高药物含量.     

Intraocular lysozyme in experimental uveitis in rabbits: aqueous and vitreous assay.

We determined normal aqueous and vitreous lysozyme levels in rabbit eyes and induced experimental uveitis to record the uppermost aqueous and vitreous lysozyme levels. The normal aqueous humor of the rabbit eye contained 1.05 mug per milliliter lysozyme and the normal vitreous humor contained 0.45 mug per milliliter. After the intravitreal administration of a foreign protein, the aqueous and vitreous lysozyme levels rose within one day, reaching maximum values of 38.4 mug per milliliter and 114 mug per milliliter, respectively, at 14 days, and subsequently declining to minimal values by 28 days after injection.     

Scleral plug of biodegradable polymers containing tacrolimus (FK506) for experimental uveitis

PURPOSE: To evaluate the efficacy of a biodegradable polymeric scleral plug containing the immunosuppressive agent, FK506, in a rabbit model for experimental uveitis. METHODS: The scleral plugs were prepared by dissolving poly(DL-lactide-co-glycolide; PLGA) and FK506 (weight, 8.5 mg; length, 5 mm; 1% FK506). The release of FK506 was evaluated in vitro by spectrophotometry on days 1, 3, 7, 14, 21, and 35. In vivo, FK506 concentrations of the vitreous were measured by high performance liquid chromatography 2 and 4 weeks after intravitreous plug implantation in pigmented rabbits. Sixteen pigmented rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, the right eyes of all rabbits were challenged with an intravitreal injection of 50 micro g of antigen. After the first challenge, the 16 eyes of 16 pigmented rabbits were divided into two groups. Scleral plugs were implanted into the vitreous of the right eye of eight rabbits. Eight control rabbits received a sham device. The aqueous protein concentrations and cell counts were determined on postchallenge days 7, 14, and 28. To simulated chronic inflammation, the eyes were rechallenged with intravitreal antigen on day 14 and were observed for 1 month. Inflammation of the anterior chamber and the vitreous were graded clinically by two masked observers. Retinal function was evaluated by electroretinography (ERG) and histologic examination. RESULTS: Clinical scores (anterior chamber cells, flare, and vitreous opacity) showed that treated eyes had significantly less inflammation than untreated eyes (P<0.001). Quantitative analysis of inflammatory cells (P<0.001) and protein concentrations (P<0.0001) in the anterior chamber showed significant decreases in treated eyes. Histopathologic examination showed marked inflammation and tissue disorganization in the untreated eyes. No retinal toxicity was detected, histopathologically and electroretinographically. After antigen rechallenge, inflammation in experimental eyes was still less than in control eyes. CONCLUSIONS: Intravitreal sustained-release of FK506 from a biodegradable polymeric scleral plug was highly effective in suppressing the inflammation of experimental uveitis in a rabbit model for at least 6 weeks. This device may be useful in the management of patients with severe chronic uveitis.     

The pathophysiology of the ocular microenvironment. II. Copper-induced ocular inflammation and hypotony

The ocular effects of intravitreally injected copper sulfate solutions were studied in New Zealand white rabbits. These injections resulted in uveitis characterized by prolonged ocular hypotony, increased protein concentrations and decreased ascorbic acid concentrations in both the vitreous and aqueous humors, and an apparent decrease in the transport function of the anterior uvea. The extent and the duration of these effects were dose-dependent. The lower doses used, 3 or 6 micrograms of Cu as CuSO4 per eye, produced reversible inflammation. The highest dose, 30 micrograms of Cu per eye, also produced some signs of ocular chalcosis: hemorrhage, vitreous liquefaction, prolonged hypotony and local iridial ischemia. Six hours after the intravitreal injection of 6 micrograms of Cu as CuSO4 per eye, the Cu concentration in the vitreous humor increased to approximately 100 times that in the vitreous of control eyes, and began to decline only 3 days later, with a half-time of approximately 8 days. The Cu concentration in the anterior chamber of these eyes never exceeded 1 ppm and returned close to control values within 3 days. Based on these findings, factors that affect ocular trace-metal distribution and kinetics are discussed, as are reasons for the apparent difficulty in diagnosing the presence of Cu-containing intraocular foreign bodies on the basis of the Cu concentration of the aqueous humor.     

Evaluation of therapeutic effectiveness using MR imaging in a rabbit model of anterior uveitis

Magnetic resonance imaging (MRI) has been used to examine conditions that alter the permeability of the blood-retinal barrier. Our goal was to determine if blood-aqueous barrier permeability could be similarly assessed, because MRI offers the theoretical advantage of providing quantitative data directly from inflamed uveal tissues rather than from the aqueous humor into which the inflammatory reaction spills. As an additional challenge, we sought to use MRI to measure differences between the inflamed uveal tissues of corticosteroid-treated and placebo-treated uveitic eyes. Anterior uveitis was induced in one eye of eight rabbits by subcutaneous injection of Mycobacterium tuberculosis, followed after 10 days with intravitreal challenge. One rabbit of each pair was treated with topical 1% prednisolone acetate while control rabbits were treated with artificial tears. Contrast-enhanced MRI studies were performed prior to uveitis induction, one day after induction and then weekly for at least 2 weeks. MR image data were analyzed to determine percent change in peak enhancement of the ciliary body and anterior chamber. The initial rate of change of enhancement of the anterior chamber was also measured. Extensive contrast agent-induced MR image enhancement of both the anterior chamber and the ciliary processes was measured following the induction of uveitis. More rapid improvement was measured for the 1% prednisolone acetate-treated rabbit eyes (P < 0.001). MR signal enhancement data obtained from the ciliary processes proved to be the most reliable indicator of disease activity in this rabbit model of uveitis. Such data can only be obtained using MRI.     

Ocular penetration of UF-021, a new prostaglandin related compound, in the rabbit eye]

The ocular penetration and pigment affinity of topically applied UF-021, a newly developed prostaglandin-related compound, were investigated in rabbit eyes using 3H-labeled UF-021. Ten minutes to 24 hours after instillation of 0.12% of 3H-UF-021 solution into New Zealand white or pigmented rabbit eyes, the rabbits were sacrificed and the eyes were immediately enucleated. The extraocular muscles, conjunctiva, aqueous humor, cornea, iris, anterior and posterior sclera, ciliary body, lens, vitreous, retino-choroid complex, optic nerve were separated and blood samples were taken. The concentration of 3H-UF-021 in each sample was determined with a liquid scintillation counter. The peak concentration of UF-021 was obtained at 40 minutes and 1 hour after instillation in the iris-ciliary body and aqueous humor of albino rabbit. According to the pharmacokinetic analysis of the data, UF-021 showed good ocular penetration into the rabbit eye, and the permeability of the epithelial barrier for UF-021 was calculated to be 2.9 x 10(-3) cm/hr. The apparent elimination rate constant and the apparent absorption rate constant were also calculated to be 0.21 hr-1 and 1.28hr-1, respectively. The time course for 3H-UF-021 concentration in the eye of pigmented rabbit was almost the same as that in the eye of non-pigmented rabbit, indicating that UF-021 did not bind to pigmented tissues.     

Synergistic uveitic effects of tumor necrosis factor-alpha and interleukin-1 beta.

Tumor necrosis factor (TNF) and interleukin-1 (IL-1), cytokines with multiple, overlapping biologic activities, have been shown to interact synergistically in nonocular tissues. To test the hypothesis that coinjection of TNF and IL-1 interact synergistically in the eye, low, marginally inflammatory doses of human recombinant TNF-alpha (4000 U), IL-1 beta (40 U), and TNF-alpha+IL-1 beta (TNF-alpha/IL-1 beta) were injected into the vitreal chamber of the rabbit eye, and inflammation was assessed at 6, 24, 48, and 168 hr post-cytokine injection. TNF-alpha/IL-1 beta induced an anterior uveitis that was barely detectable at 6 hr, increased at 24 hr, peaked at 48 hr, and largely resolved by 168 hr. Synergy was observed for infiltration of inflammatory leukocytes into aqueous humor at 24 and 48 hr and for protein and prostaglandin E levels in aqueous humor at 48 hr. Based upon protein levels in vitreous humor, TNF-alpha/IL-1 beta also induced a posterior uveitis. This posterior uveitis was not apparent until 48 hr and then increased significantly at 168 hr. At 48 and 168 hr, the effects of TNF-alpha/IL-1 beta on protein levels in vitreous humor were consistent with a synergistic interaction. Results of separate experiments using higher dose combinations of TNF-alpha/IL-1 beta and a longer time course suggested that the effects of TNF-alpha/IL-1 beta on the blood vitreous barrier persisted beyond 168 hr. The results of this study support the hypothesis that TNF-alpha and IL-1 beta interact synergistically when injected into the rabbit eye.(ABSTRACT TRUNCATED AT 250 WORDS)