Pars plana vitrectomy assisted by triamcinolone acetonide for refractory uveitis: a case series study.

AIM: To examine the outcome of a triamcinolone acetonide (TA) assisted pars plana vitrectomy (PPV) for refractory uveitis. METHODS: Six patients suffering from proliferative vitreoretinopathy (PVR) with refractory uveitis underwent a TA assisted PPV. The patients consisted of one with Vogt-Koyanagi-Harada disease, one with acute retinal necrosis, one with Behçet's disease, and three with sarcoidosis. TA was inoculated into the vitreous cavity to visualise the vitreous. In four of six patients, 4 mg of TA were intentionally left in the vitreous cavity to reduce the degree of postoperative inflammation. RESULTS: The vitreous body was clearly seen using TA during surgery, which greatly helped us to perform a posterior hyaloid resection safely and thoroughly. As we previously observed in other disease, TA allowed us to visualise the transparent vitreous and thus was helpful in removing the vitreous cortex from the retina completely in uveitis. One patient (Behçet's disease, in whom TA was intentionally left) showed an elevated intraocular pressure (IOP) transiently after surgery which was controllable by topical eye drops. The remaining TA diminished day by day and had almost completely disappeared within a month from operation. CONCLUSION: TA improved the visibility of the hyaloid and the safety of the surgical procedures and no serious complications were observed after TA assisted PPV in uveitis. Although the long term effects are still unknown, this method appears to be potentially useful as an improved treatment for PVR associated with refractory uveitis.

Electroporation and bleomycin in glaucoma-filtering surgery.

PURPOSE: To develop a new treatment in glaucoma-filtering surgery using combined treatment with electroporation and the antiproliferative drug bleomycin. METHODS: Pigmented rabbits were treated with both bleomycin (10 micrograms/ml) and localized electric pulses (EP) using a special probe (5 V/cm, 100 msec, 8 pulses) (n = 10; group A). After EP treatment, bleomycin was washed out with 50 ml balanced salt solution, and then a posterior lip sclerectomy was performed on the same area. We also studied rabbits undergoing a posterior lip sclerectomy with bleomycin treatment alone (n = 10; group B), a posterior lip sclerectomy with EP treatment alone (n = 5; group C) and a posterior lip sclerectomy alone using the same operation (n = 5; group D, negative control). The intraocular pressure (IOP) was measured before and 1, 3, 5, 7, 10, 15, and 20 days after surgery. The formation of blebs, the conjunctiva, and the cornea were periodically examined by slit-lamp biomicrography. RESULTS: In every group, the IOP decreased until day 7, and no significant difference was observed among the four groups. In groups B, C, and D (control), the IOP increased gradually from day 10 and thereafter returned to the preoperative level after 15 days. However, in group A, the IOP remained lower than the preoperative level for 20 days; it was also significantly lower than each of the other three groups (P < 0.01). The survival rate of a filtering bleb was significantly higher in group A than in groups B, C, or D, but the survival rate in group B was not higher than groups C or D. No adverse effects were clinically observed in the ocular tissue, such as the cornea and conjunctiva. CONCLUSIONS: The combined treatment with EP and bleomycin was found to decrease IOP more prominently than EP or bleomycin treatment alone in filtering surgery. This treatment thus makes filtering surgery effective by decreasing the dose of the antiproliferative drug and by possibly localizing the drug delivery.

Immunomodulation of experimental autoimmune uveoretinitis by intravenous injection of uveitogenic peptides.

Intravenous (IV) injection of antigenic proteins induces specific unresponsiveness, as shown by the diminished response to a challenge with these proteins in complete Freund's adjuvant. This study examined the effect of IV treatment with uveitogenic peptides on the development of experimental autoimmune uveoretinitis (EAU). The peptides used were derived from the sequence of bovine interphotoreceptor retinoid-binding protein (IRBP) and included R16 (sequence, 1177-1191), which is immunodominant and highly uveitogenic, and R4 (sequence, 1158-1180), which is nondominant and weakly uveitogenic. The efficacy of this treatment was found to depend on both the dose used for the IV injection and that used for the challenge. Thus, EAU induced by R16 at a dose of 0.2 nmol/rat was inhibited completely in all rats treated with the peptide at doses of 400 or 133 nmol and partially by the low dose of 5 nmol/rat. However, the EAU induced by a R16 challenge of 40 nmol/rat was inhibited only partially by the high treatment dose of 400 nmol/rat. The IV treatment was found to be effective in inhibiting the EAU induced by peptide R4. A large dose of R4 was needed to induce EAU (40 nmol/rat), and the disease was inhibited completely in all rats treated IV with this peptide at doses of 800, 400, or 133 nmol. In most animals injected with the 44-nmol dose, also, inhibition was complete. These data show that there is a correlation between the doses needed for achieving inhibition and those used for the challenge. The ratios between these doses in all experiments were found within the range 1-20.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-metastatic effect by in vivo administration of concanavalin A through augmentation of T-derived activated killer activity: efficacy to B16 melanoma expressed MHC antigen.

We attempted to investigate if the in vivo administration of concanavalin A (Con A), a potent T cell stimulator, would render anti-metastatic activity in hosts. Assays of activity were performed 20 days after iv inoculation of two clones of the B16 melanoma, B16-H (H-2+, highly metastatic), B16-L (H-2-, low metastatic), or 3LL cells into C57BL mice by enumerating lung colonies. In some experiments, hosts treated with anti-asialo GM1 Ab were used to evaluate effector mechanisms other than NK cells. While the injection of Con A alone had no significant effect on anti-metastatic activity, in nonimmunized hosts the effect by Con A was displayed when the mice were preimmunized with B16-H cells but not in those immunized with B16-L cells. Immunization with B16-H or B16-L cells alone resulted in the generation of killer cells with promiscuous lytic activity and induced an anti-metastatic effect against B16-H, B16-L, and 3LL cells. Con A treatment significantly augmented the killer activity of spleen cells of mice preimmunized with B16-H cells but not of those immunized with B16-L cells. The effectors from mice immunized with B16-H alone or given both Con A and B16-H were mainly of Thy 1+ Lyt2+ asialo GM1- cells, on the other hand, those from mice immunized with B16-L cells expressed asialo GM1 antigen. We showed the efficacy of Con A on the anti-metastatic effect in relation to the host immune response.

AK cells were developed from NK cells during in vitro culture of allogeneic or F1 anti-parental stimulation: functional conversion in recognizing H-2 expression of target cells accompanied by phenotypical conversion.

In vitro sensitization of (CBA x A)F1 spleen cells for 3 days with allogeneic C57BL cells raised the killer activity to the NK-sensitive YAC-1 target. When (A x C57BL)F1 spleen cells were cultured with parental C57BL cells, the lytic activity to YAC-1, P815 and EL-4 targets occurred on Day 6 after the culture. Phenotypical analyses showed that these culture-activated killer (AK) cells were derived from asialo-GM1+Thy-1-NK cells; however, they expressed Thy-1 antigen but not asialo-GM1 antigen at the effector cell level. Generation of the AK cells was not evident in cultures of spleen cells from mice with a neonatally induced tolerance to stimulator antigen and in those from T-cell-depleted mice. The supernatant of allostimulated culture, which contained a low concentration of IL-2, rendered the above cells capable of evoking AK activity. The H-2-reduced target cells were sensitive to NK cells, but less sensitive to AK cells; on the contrary, the H-2 highly expressed cells (interferon-treated cells) were less susceptible to NK cells but highly susceptible to AK cells. Thus, the relation between NK susceptibility and susceptibility to AK cells is inverse. Our study shows that stimulation with lymphokines causes a functional conversion accompanied by a phenotypical conversion of NK cells. With reference to immunosurveillance, these observations lead to the idea that NK and AK cells represent two functionally distinct but complementary systems involved in cell-mediated immunosurveillance.