Antithrombotic effect of ticlopidine in an experimental model of retinal vein occlusion.

PURPOSE: Ticlopidine inhibits adenosine diphosphate (ADP)-induced platelet aggregation and may be effective in patients with retinal vein occlusions (RVO). This study tests the efficacy of ticlopidine in an animal model of RVO. METHODS: Rose bengal-mediated argon laser photothrombosis of retinal veins was created in rabbits pretreated with oral ticlopidine, aspirin, or saline. The number of laser spots necessary to produce a partial or complete RVO was recorded and tabulated. RESULTS: Pretreatment with ticlopidine significantly increased the number of laser spots needed to produce a partial (P =.02), or a complete (P =.002) RVO as compared to the control group. Pretreatment with ticlopidine significantly increased the number of laser spots needed to produce a partial RVO (P =.02). Pretreatment with aspirin significantly increased the number of laser spots needed to produce a complete RVO (P =.002). CONCLUSION: Ticlopidine may be a useful antiplatelet agent for the treatment of patients with RVO. Patients treated with ticlopidine should be monitored for the possible development of hematologic disorders.

Photocrosslinkable polysaccharides for in situ hydrogel formation.

In situ photopolymerization is an exciting new technique for tissue engineering. Two photocrosslinkable polysaccharides composed of alginate and hyaluronan are described that upon photolysis form soft, flexible, and viscoelastic hydrogels. The degree of methacrylate modification and thus covalent affects mechanical properties such as swelling, compression, and creep compliance. Significant swelling is observed in aqueous solution; these hydrogels can swell up to 14 times their dry weight. Both hydrogels exhibit low phase angles and (G*) values indicative of viscoelastic materials. The hyaluronan based hydrogel is stronger and more resilient than the corresponding alginate gel. SEM and AFM studies on both hydrogels show smooth and uniform surfaces at the macroscopic level with salient features observed only on the nanometer scale. Rapid polymerization by an optical trigger allows for controlled in situ photopolymerization in a minimally invasive manner, indicating that these hydrogels are relevant for biomedical applications such as sealing wounds and reconstructing soft tissues.

Sloughing of corneal epithelium and wound healing complications associated with laser in situ keratomileusis in patients with epithelial basement membrane dystrophy.

PURPOSE: To report sloughing of corneal epithelium during laser in situ keratomileusis and subsequent wound healing complications in patients with epithelial basement membrane dystrophy. METHODS: In a retrospective study, the surgical procedures, postoperative course, and visual acuities of 16 eyes of nine patients with epithelial basement membrane dystrophy who underwent laser in situ keratomileusis complicated with epithelial sloughing at three centers were reviewed. The mean follow-up period was 23 weeks (range, 4 to 52 weeks). RESULTS: In 13 (81%) of 16 eyes with epithelial basement membrane dystrophy, epithelial sloughing occurred during laser in situ keratomileusis. In eight of the 13 eyes, epithelial growth beneath the flap was observed. The flap was lifted and the interface epithelium scraped in six eyes. Flap melt or keratolysis occurred in four eyes. At the last follow-up visit, 13 of 16 eyes had an uncorrected visual acuity of 20/30 or better, and all eyes had a best-corrected visual acuity of 20/30 or better. CONCLUSIONS: Patients with epithelial basement membrane dystrophy have poorly adherent corneal epithelium and are predisposed to epithelial sloughing during the microkeratome pass of laser in situ keratomileusis. This may lead to flap distortion, interface epithelial growth, flap keratolysis, and corneal scarring. It is not recommended that laser in situ keratomileusis be performed in patients with classic, symptomatic epithelial basement membrane dystrophy. In patients who present with mild and asymptomatic epithelial basement membrane dystrophy, laser in situ keratomileusis should be performed with caution, or photorefractive keratectomy may be the preferred refractive procedure.

Suppressive effect of transforming growth factor beta1 on the recurrence of experimental melanin protein-induced uveitis: upregulation of ocular interleukin-10.

Uveitis is induced in Lewis rats by immunization with bovine melanin protein (BMP) derived from the uvea and retinal pigment epithelium. Recurrence of this experimental melanin protein-induced uveitis (EMIU) develops after footpad injection of a minimal amount of Salmonella typhimurium endotoxin (LPS) following the remission of EMIU. To investigate the effect of transforming growth factor beta1 (TGFbeta1) on the recurrence of EMIU, 5 micrograms LPS booster was given to Lewis rats by footpad injection on Day 45 after BMP immunization. Daily TGFbeta1 or phosphate-buffered saline was administered either from Day 0 to 7 (group 1) or from Day 7 to 13 (group 2) after LPS booster. Delayed-type hypersensitivity (DTH) ear test was conducted on Day 12 after LPS booster and eye and blood were collected on Day 14. The incidence and severity of recurrent uveitis markedly decreased in both groups of TGFbeta1-treated rats. A lower level of serum BMP antibody was also observed by agglutination in these groups. There was no statistical difference in DTH responses between the treated and control groups. Ocular cytokine mRNA of group 1 and controls was analyzed by RT-PCR. Interleukin (IL)-2 and interferon-gamma were not detectable. IL-4 was identified at a similar level in both groups. A higher level of IL-10 was observed in group 1 rats. We conclude that TGFbeta1 suppresses recurrent EMIU, probably through upregulation of IL-10.

A clinicopathologic report of the retinal lesions associated with didanosine.

Didanosine, a purine analogue with antiretroviral activity, is used in the treatment of human immunodeficiency virus disease. Associated toxic effects of didanosine include pancreatitis, peripheral neuropathy, and retinopathy. The retinal lesions associated with didanosine therapy were studied in a 6-year-old girl with acquired immunodeficiency syndrome. Gross examination disclosed multiple well-circumscribed depigmented lesions in the midperipheral retina. Microscopic examination of these lesions showed multiple areas of retinal pigment epithelial (RPE) loss, some surrounded by areas of hypertrophy or hypopigmentation of the RPE. Partial loss of the choriocapillaris and neurosensory retina were also noted in areas of diseased RPE. Transmission electron microscopy showed numerous membranous lamellar inclusions and cytoplasmic bodies in the RPE cells. These data show that didanosine primarily affects the RPE and that the choriocapillaris and overlying neurosensory retina are also dystrophic in areas of RPE loss.

Ocular inflammation stimulated by the immunomodulator AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate].

The purpose of this study was to investigate the effect of a novel immunomodulator, AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate], in the eye. Lewis rats were injected intravitreally with AS101 at a concentration of 13 micrograms/ml in one eye and BSS in the contralateral eye. Control animals were injected with BSS into the central vitreous of both eyes. Ocular inflammation was evaluated at 20 hours by histology, immunopathology, and by cell count, protein and cytokine measurement in the aqueous humor. At 20 hours, eyes injected with AS101 developed iridocyclitis and mild vitritis versus minimal inflammation and/or protein in contralateral eyes or eyes of control animals (p = 0.0121). The inflammatory infiltrate was mixed in character. Major Histocompatibility Complex (MHC) class II antigens and intercellular adhesion molecules (ICAM-1) were expressed in the anterior segment of eyes injected with AS101. In the aqueous humor of these eyes there were significant quantities of inflammatory cells, protein (mean +/- SEM = 11.2 +/- 2.3 mg/ml) and the cytokine interleukin 6 (IL-6) (450 units/ml) compared with contralateral eyes (p = 0.0005 for inflammatory cells; protein, mean +/- SEM = 1.6 +/- 0.17 mg/ml; IL-6 = 12 units/ml) and both eyes of control animals injected with BSS (p = 0.8955 for inflammatory cells; protein, OD = 1.5 mg/ml, OS = 0.7 mg/ml; IL-6, OD = 8 units/ml, OS = 13 units/ml). AS101 has a local inflammatory effect in the eye. This compound may activate ocular inflammation by releasing cytokines such as IL-6.

Experimental melanin-protein-induced uveitis in the Lewis rat. Immunopathologic processes.

PURPOSE: To study the immunopathology of experimental melanin-protein-induced uveitis in the Lewis rat. METHODS: Rats were immunized with bovine ocular melanin protein. The kinetics of experimental melanin-protein-induced uveitis was studied by clinical examination and immunopathology. Cellular and humoral responses were evaluated by lymphocyte proliferation, delayed-type hypersensitivity, and agglutination. After clinical disease subsided, recurrent experimental uveitis was induced with a low-dose footpad injection of lipopolysaccharide. RESULTS: Experimental melanin-protein-induced uveitis was characterized by bilateral uveal infiltration mainly with lymphocytes and monocytes. Delayed-type hypersensitivity, lymphocyte proliferation, and agglutination to bovine ocular melanin protein were positive. Expressions of major histocompatibility complex class II and intercellular adhesion molecule-1 were observed before ocular infiltration. The predominantly infiltrating cells were CD4+ lymphocytes. Experimental melanin-protein-induced uveitis subsided within 1 month, spontaneously recurred within 1 week in approximately one quarter of the rats, and was inducible in most rats with 5 micrograms of lipopolysaccharide confirmed by histopathology. CONCLUSIONS: Experimental melanin-protein-induced uveitis is a T-cell-mediated autoimmune uveitis, resembling noninfectious recurrent iridocyclitis and choroiditis in humans.

Granulomatous reaction to Bruch's membrane in age-related macular degeneration.

The histopathologic features of a granulomatous reaction in one eye of a patient with neovascular age-related macular degeneration are presented. Multiple multinucleated giant cells were found in intimate association with Bruch's membrane and at the margin of Bruch's membrane defects. Multinucleated giant cells appear to participate in the breakdown of Bruch's membrane and, together with diffuse disease of the retinal pigment epithelium and changes in the physicochemical properties of Bruch's membrane, may provide angiogenic stimulus for choroidal neovascularization in age-related macular degeneration.

Clinicopathologic correlation of the multiple recurrent serosanguineous retinal pigment epithelial detachments syndrome.

PURPOSE: Ocular clinicopathologic correlation in a patient with bilateral multiple recurrent hemorrhagic detachments of the sensory retina and retinal pigment epithelium (RPE), which eventually led to rubeosis and loss of useful vision in one eye, is described. The clinical appearance was most consistent with multiple recurrent serosanguineous RPE detachments syndrome (which may be similar to posterior uveal bleeding, or PUB, syndrome). METHODS: Light microscopic examination of 450 serial sections through a 3.7-mm area including the macula, optic nerve head, and superior and inferior peripapillary region of the eye that underwent diagnostic enucleation was performed. One fresh cap was used for immunohistochemical staining. Tissue from the posterior aspect of the other cap was prepared for electron microscopy. RESULTS: Microscopic examination disclosed extensive fibrovascular proliferation in the subretinal space and within Bruch's membrane, and the presence of at least 23 choroidal blood vessels that traversed defects in Bruch's membrane. Immunohistochemical studies of inflammatory infiltrates within the choroid and fibrovascular tissue demonstrated both a B- and T-cell response. CONCLUSION: In this case, recurrent serosanguineous detachments of the sensory retina and RPE were secondary to choroidal neovascularization with extensive fibrovascular proliferation in the subretinal space and within Bruch's membrane. Marked lymphocytic infiltration was present throughout the choroid and the fibrovascular tissue. Clinical improvement in the fellow eye after immunosuppressive therapy suggested that an immunologic component might be a causative factor, although the waxing and waning course in this condition precludes any definitive evaluation for its use in multiple recurrent serosanguineous RPE detachments syndrome.

Clinicopathologic correlation of laser lesion expansion after treatment of choroidal neovascularization.

The clinicopathologic features of photocoagulation lesion expansion after two separate sessions of krypton red laser for choroidal neovascularization (CNV) in an eye with age-related macular degeneration are presented. The area of expansion is characterized by retinal pigment epithelial atrophy and loss of the photoreceptor cell layer. A thin margin of retinal pigment epithelium hypopigmentation and variable photoreceptor cell layer degeneration also borders the lesion in some areas.