Dietary Lactobacillus casei can be used to influence intraepithelial lymphocyte migration and modulate mucosal immunity in chicks.

1. The role of probiotics in modulating intestinal mucosal immunity in chicks was investigated by measuring migration of intraepithelial lymphocytes (IEL) and cytokine signals in chicks fed on a diet supplemented with the Lactobacillus casei compared with those of chicks fed on an unsupplemented diet.2. Increased numbers of intraepithelial lymphocytes (IEL) were detected in the ileal epithelium at d 3 and d 7 after feeding a diet containing 108 CFU/g L. casei.3. Greater expression of chemokine genes for C-C motif chemokine ligand 3, C-X-C motif chemokine ligand 12, C-C motif chemokine receptor 5, and C-C motif chemokine receptor 9 were detected in the ileum on d 3, suggesting a greater number of IEL was associated with lymphocyte migration through the chemokine signalling pathway.4. After IEL migration, cell proliferation was evident in mucosal epithelial cells on d 14. Evidence of immune responses induced in the ileum from d 3-21 after feeding the diet containing L. casei was shown by the significant (P < 0.05) differences in transforming growth factor-ß, secretory immunoglobulin A, interferon-γ, tumour necrosis factor-α, interleukin-4, and interleukin-10.5. These results indicated that feeding L. casei helps guide IEL migration and modulates intestinal mucosal immunity.

Combined intravitreal anti-VEGF and verteporfin photodynamic therapy for juxtafoveal and extrafoveal choroidal neovascularization as an alternative to laser photocoagulation.

PURPOSE: To evaluate anti-VEGF and photodynamic therapy (PDT) for juxtafoveal and extrafoveal choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD), ocular histoplasmosis syndrome (OHS), and degenerative myopia. METHODS: A total of 10 eyes with juxtafoveal or extrafoveal choroidal neovascularization underwent intravitreal anti-VEGF therapy combined with verteporfin PDT (689 nm). Most treatments consisted of PDT every 12 weeks and either ranibizumab 0.5 mg every 4 weeks or bevacizumab 1.25 mg every 6 weeks, initiated concurrently. Retreatment criteria were persistent exudative signs on optical coherence tomography or fluorescein angiography. RESULTS: Presenting visual acuity (VA) ranged from 20/20 to 20/60 (mean log MAR+/-SD, 0.338+/-0.16 (20/44 equivalent)). After a mean follow-up of 17.5 months, it ranged from 20/15 to 20/40 (mean log MAR+/-SD, 0.150+/-0.14 (20/28 equivalent); P=0.027, paired t-test). Six eyes improved by > or = 2 lines and four remained within 2 lines of initial VA. Non-ARMD eyes required much fewer treatments than ARMD eyes. All five non-ARMD eyes and three of five ARMD eyes showed no CNV activity at least 5 months after last treatment. CONCLUSIONS: Anti-VEGF therapy and PDT can preserve good visual function and may be suited to some cases of nonfoveal CNV. ARMD eyes require longer courses of treatment than non-ARMD eyes.

Sustained postoperative face-down positioning is unnecessary for successful macular hole surgery.

AIM: To determine the rate of successful macular hole closure with 1-day postoperative prone positioning METHODS: Multicentre review of all consecutive cases of stage 3 and 4 macular hole surgery performed during a 15-month period employing 1-day postoperative face-down positioning regimen. Cataract surgery was not routinely combined with macular hole surgery. Internal limiting membrane peeling was employed in all but seven eyes. Either SF6 or C3F8 gas tamponade was used. The primary outcome assessed was the rate of hole closure. RESULTS: 56 eyes of 53 patients were identified. 79% of eyes had stage 3 macular holes, and 39 of 56 (70%) eyes were phakic at the time of surgery. The mean preoperative logMAR vision was 0.74 (approximately 20/100 Snellen) and mean postoperative logMAR vision was 0.41 ( approximately 20/50 Snellen) with a mean follow-up period of 5.2 months. Macular hole closure was achieved in 52 eyes (93%) with one operation. CONCLUSION: Sustained postoperative face-down positioning may not be necessary for successful macular hole closure, since 93% of eyes achieved hole closure with prone positioning for only 1 day.

Radiologic findings in infected and noninfected scleral buckles.

PURPOSE: To present the radiologic findings in scleral buckle infections and in the early postoperative period after scleral buckling. METHODS: Retrospective multicenter orbital computed tomography (CT) study of 14 patients and brain magnetic resonance (MR) in one patient with scleral buckle infections, some with the referring diagnosis of endophthalmitis, proliferative vitreoretinopathy, orbital cellulitis, or unilateral headache. The control population consisted of early postoperative prospective CT study of 38 consecutive patients with scleral buckle without clinical infection. RESULTS: Diffuse scleral thickening and preseptal soft tissue swelling were noted in acute scleral buckle infections. Scleral thickening decreased radiologically following prompt antibiotic therapy in five patients with acute infections. Silicone sponge had low attenuation without infection and high attenuation with infection. In chronically infected scleral buckle, the sclera was thickened around the buckle, with scleral melt under the buckle. MR showed increased signal intensity in the preseptal region in one patient with chronic fungal infection. In the controls, two had thickening of the sclera without soft tissue swelling. CONCLUSIONS: CT or MR can assist in the early diagnosis and management of scleral buckle infections.

Vitrectomy for large vitreous opacity in retinitis pigmentosa.

PURPOSE: To describe a patient with bilateral retinitis pigmentosa and visually disabling vitreous opacities, who benefited from vitrectomy in both eyes. METHODS: A 37-year-old man with retinitis pigmentosa and severely constricted visual fields developed a large, dense, vitreous floater and visual obscuration in the right eye. Subsequently, diffuse vitreous opacification and visual obscuration developed in the left eye. RESULTS: Bilateral pars plana vitrectomy relieved the patient's visual obscurations. Electron micrographs of the excised vitreous opacity from the left eye showed collagen fibrils and cellular debris. CONCLUSION: Visually significant vitreous opacities may develop as a complication of retinitis pigmentosa. The visual impact of such opacities may be magnified by its superimposition on limited visual fields. Vitrectomy may be of benefit in such cases.

Mutation of Ha-ras Oncogene in Rat Salivary Gland Tumors Induced by DMBA.

PURPOSE: The incidence of salivary gland tumor is approximately 2% among all head and neck tumors, of which malignant cases account for only about 5%. Much research has been performed in order to clarify the mechanism of oncogene activation, however salivary gland tumors remain understudied. We performed this study in order to characterize the ras gene in these tumors. MATERIALS AND METHODS: We treated white rats with 7, 12-dimethylbenz[a]anthracene (DMBA) and confirmed the occurrence of salivary gland tumors after ten to thirty weeks. Isolated genomic DNAs from tumor tissues were added to NIH 3T3 cells. In order to detect Ha-ras mutations, we performed a two-step PCR-RFLP and 7analyzed the mutated sequences. RESULTS: We induced salivary gland tumors by DMBA treatment in white rats. Isolated DNAs from the tumor tissues transformed the NIH 3T3 cells. Point mutations were observed in codons 12 and 61 of the Ha-ras oncogene. The total frequency of point mutations was 13.9% in DMBA-induced salivary gland tumors in rats. CONCLUSION: Our results demonstrate that a variety of cancers ras oncogene mutations were also found in salivary gland tumors. We confirmed that a point mutation of the Ha-ras oncogene in a DMBA-induced salivary gland tumor occurs at a frequency of 13.9%.

Development of a safe and rapid neutralization assay using murine leukemia virus pseudotyped with HIV type 1 envelope glycoprotein lacking the cytoplasmic domain.

Neutralizing antibody (NAb) is a critical component of an immune system that can potentially provide sterilizing protection against human immunodeficiency virus type 1 (HIV-1). Therefore, an in vitro assay that can rapidly, safely, and accurately evaluate the NAb response vaccine candidates elicit, especially against a large number of HIV-1 variants, would be highly valuable. It has been demonstrated that HIV-1 envelope glycoprotein lacking the cytoplasmic domain can pseudotype murine leukemia virus encoding the beta-galactosidase gene and that this pseudovirus can specifically infect CD4(+) cells (Schnierle BS, Stitz J, Bosch V, et al.: Proc Natl Acad Sci USA 1997;94:8640-8645). Because the pseudovirus is not biohazardous and because the infection can be quantitatively determined within 2 days, we examined the feasibility of using the pseudovirus for high-throughput neutralization assays for HIV-1. We have generated viruses pseudotyped with gp140 of six different HIV-1 isolates (LAI, RF, Bal, AD8, 89.6, and DH12). All six pseudoviruses were infectious and exhibited expected coreceptor usage phenotype in HOS-CD4 cells expressing either CCR5 or CXCR4. More importantly, the neutralization sensitivity profile of these pseudoviruses was virtually identical to that observed from more conventional neutralization assays using either HIV-1 or SHIV. All pseudoviruses could be neutralized by broadly reactive human monoclonal antibody IgG1 b12. Our results indicate that the pseudoviruses are ideal for high-throughput evaluation of immune sera for their capacity to broadly neutralize a large number of HIV-1 isolates.

Transpupillary thermotherapy of occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in management of occult subfoveal choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). METHODS: Retrospective chart review of eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line and final ETDRS visual acuity and fluorescein angiography (FA) were compared. RESULTS: For the 48 eyes which met inclusion criteria, mean pre-operative visual acuity was 20/128 (range: 20/50-20/500). Average follow-up was 27 weeks (range: 12 weeks-55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18 eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted during treatment. Three eyes developed large submacular hemorrhage within 2 months of treatment. Based on clinical examination and FA, 61% of the eyes appeared to have reduction of subretinal fluid compared to pre-operative evaluations. CONCLUSION: Visual acuity was stable or improved in 62.5% of eyes in our series and the treatment was well tolerated. Longer follow up and larger number of patients would be required to evaluate the ultimate benefit of TTT in management of occult CNV due to AMD.

Ocular findings in aplastic anemia.

OBJECTIVE: To analyze the ocular findings in aplastic anemia. DESIGN: Eighteen patients with aplastic anemia were examined. RESULTS: Ocular findings included cotton wool spots (38%), nerve fiber layer or preretinal hemorrhages (67%), vitreous hemorrhages (13%), a picture resembling central retinal vein occlusion (13%) and optic disk edema (6%). Preretinal hemorrhages were the presenting sign of aplastic anemia in 2 patients (13%). CONCLUSIONS: A blood profile is needed in patients with unexplained retinal hemorrhages. Patients with aplastic anemia need to avoid ocular massage and Valsalva maneuvers to decrease ocular morbidity.

Complications of pneumatic retinopexy.

Pneumatic retinopexy is a retinal reattachment procedure involving transconjunctival injection of gas into the vitreous cavity, combined with cryotherapy or laser retinopexy and followed by postoperative positioning. Although generally a safe procedure, it may be associated with certain adverse outcomes. These most commonly include misplaced gas injection, subretinal gas, vitreous hemorrhage, new retinal breaks, failure to reattach the retina, proliferative vitreoretinopathy, and delayed reabsorption of subretinal fluid. Less common problems include endophthalmitis, macular folds, angle-closure glaucoma, and macular hole. In most cases, complications are successfully managed, and a favorable outcome is achieved.

Relentless placoid chorioretinitis: A new entity or an unusual variant of serpiginous chorioretinitis?

OBJECTIVE: To characterize an unusual clinical entity resembling acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis but with an atypical clinical course. PATIENTS: We describe 6 patients, aged 17 through 51 years, exhibiting this unusual entity who were seen at 6 different centers from 1984 to 1997. RESULTS: The acute retinal lesions in this series were similar to those of APMPPE or serpiginous choroiditis, both clinically and on fluorescein and indocyanine green angiography. However, the clinical course, number of lesions, and location of these lesions were atypical. These patients had evidence of numerous posterior and peripheral retinal lesions predating or occurring simultaneously with macular involvement. Older, healing pigmented lesions were often accompanied by the appearance of new active white placoid lesions. Additionally, these cases all demonstrated prolonged periods of activity resulting in the appearance of more than 50 and sometimes hundreds of lesions scattered throughout the fundus. Growth of subacute lesions and the appearance of new lesions continued for 5 to 24 months after initial examination, and relapses were common. CONCLUSIONS: This entity has clinical features similar to APMPPE and serpiginous choroiditis but has a prolonged progressive clinical course and widespread distribution of lesions. It may represent a variant of serpiginous choroiditis or may be a new entity. We call it relentless placoid chorioretinitis. Arch Ophthalmol. 2000;118:931-938

The new genotypic human calicivirus isolated in Seoul.

A new type of human calicivirus (HuCV) showing the classic cup-shaped surface morphology was identified in the stool sample from a child with symptoms of acute gastroenteritis in Seoul, Korea (SK virus). Genomic RNA was extracted directly from the stool sample, and the nucleotide sequence of 3.2 kb of the 3' end of SK virus was determined from cDNA. This region spanned sequences from the RNA-dependent RNA polymerase (RDRP) region in the open reading frame 1 (ORF1) to the 3' poly A tail. The non-structural and capsid protein coding sequences were fused in a single ORF as observed in Manchester type (Genogroup III). However, ORF2 of Manchester virus was missing in SK virus. In RDRP region, SK virus showed amino acid and nucleotide identities of 74-75% and 68-69% respectively, with those of Manchester virus, while showed 34-46% and 55-60% identities respectively with those of other human caliciviruses. However, capsid protein of SK virus showed a partial (29-46%) amino acid identity with those of other caliciviruses including Manchester type. The closest resemblance in amino acid (97-99%) and nucleotide sequence (85-86%) identities were found in RDRP region with Vanderbijlpark and Pretoria isolates recently found in South Africa. These results suggest that SK virus together with Vanderbijlpark and Pretoria isolates belong to a new type different from Manchester virus.

Vitrectomy update for macular traction in ocular toxocariasis.

PURPOSE: To study the results of modern vitrectomy in traction and combined traction-rhegmatogenous retinal detachment involving the macula in cases of ocular toxocariasis. METHODS: This was a cohort study of patients seen in different institutions in the United States. Ten eyes of 10 patients were studied. Vitrectomy was performed in all eyes, combined with membrane removal, scleral buckle, fluid-gas exchange, silicone oil, or lensectomy in certain cases. The anatomic and visual results of surgery were reviewed. RESULTS: Ten eyes from 10 patients ranging in age from 2 to 33 years (median, 6 years) were reviewed. Follow-up ranged from 3 months to 8 years (median, 2 years). All eyes achieved macular attachment following surgery; vision improved in 5 (50%) eyes, and was unchanged in 5 (50%). Histologic specimens from six eyes were reviewed, and revealed combinations of fibrous tissue, eosinophils, plasma cells, lymphocytes, and giant cells. One specimen revealed an encysted Toxocara canis organism. CONCLUSION: Inflammation created in response to Toxocara larvae may lead to traction retinal detachment of the macula. Vitreoretinal surgery has a good chance of reattaching the macula and improving vision.

The use of topical aqueous suppressants in the prevention of postoperative intraocular pressure elevation after pars plana vitrectomy with long-acting gas tamponade.

OBJECTIVE: To determine whether topical aqueous suppressant therapy applied after pars plana vitrectomy with gas tamponade prevents postoperative intraocular pressure (IOP) elevation. DESIGN: Prospective, nonrandomized comparative study. PARTICIPANTS: Forty-one patients who met inclusion criteria and underwent pars plana vitrectomy with gas tamponade (SF6 18%-20% or C3F8 12%-16%) over a 1-year period. INTERVENTION: Treatment eyes received topical aqueous suppressants at the end of surgery. MAIN OUTCOME MEASURES: Postoperative IOP at 4 to 6 hours, 1 day, and 1 week. RESULTS: Twenty-one control and 20 treatment eyes met the inclusion criteria. The IOP (in mmHg) measured at 4 to 6 hours (23.05 [control, 14.73 [treatment]) and 1 day (23.24 [control], 17.28 [treatment]) postoperatively showed a statistically significant difference between the groups (P = 0.0038) at 4 to 6 hours and a trend toward significance (P = 0.057) at 1 day. Eleven control and three treatment eyes had an IOP spike above 25 mmHg at 4 to 6 hours or 1 day postoperatively (P = 0.02), and six control eyes and one treatment eye had postoperative IOP greater than 30 mmHg. A pressure rise greater than 40 mmHg was seen in two control eyes and no treatment eyes. CONCLUSIONS: Use of topical aqueous suppressants after pars plana vitrectomy with long-acting gas tamponade is effective in preventing significant postoperative IOP elevation in most cases.

A study of surgical approaches to retinal vascular occlusions.

OBJECTIVE: To develop a surgical approach to retinal vascular occlusive diseases. METHODS: Surgical manipulations were performed on the retinal vasculature to explore the feasibility of retinal vascular surgery. In a human cadaver eye model (25 procedures, 21 eyes), we performed (1) cannulations of retinal blood vessels with a flexible stylet and (2) arteriovenous sheathotomies. Histological findings were correlated with surgical outcomes. In an in vivo model (6 eyes, 5 animals), we examined the technical feasibility and anatomical outcome of surgical penetration of retinal blood vessels. RESULTS: Cannulations of branch retinal arterioles were successful in 7 of 9 procedures, cannulations of branch retinal venules were successful in 1 of 3 procedures, cannulations of central retinal arteries were successful in 0 of 2 procedures, and cannulations of central retinal veins were successful in 2 of 4 procedures. Arteriovenous sheathotomies were successful in 4 of 7 procedures. In the in vivo model, surgical penetration of retinal blood vessels was accomplished in 5 of 6 eyes. Immediately postoperatively, thrombus formation with obstruction of the retinal vasculature was observed. At 2 weeks postoperatively, the retinal vasculature was completely patent. CONCLUSIONS: Multiple surgical techniques aimed at assisting recanalization of occluded retinal vasculature have been evaluated. Retinal vascular surgery has become more feasible and deserves further investigation.

Endophthalmitis from Mycobacterium bovis-bacille Calmette-Guérin after intravesicular bacille Calmette-Guérin injections for bladder carcinoma.

PURPOSE: To present clinical and histologic findings of intraocular infection with Mycobacterium bovis-bacille Calmette-Guérin after intravesicular bacille Calmette-Guérin injections for treatment of bladder carcinoma. METHODS: A 77-year-old man was initially seen with visual acuity of 20/200, focal retinitis, vasculitis, and progressive vitreous opacity in the right eye and visual acuity of light perception, intraocular inflammation, and a dense cataract in the left eye 14 months after intravesicular injection of live bacille Calmette-Guérin organisms. RESULTS: Vitreous cultures in the right eye demonstrated growth of bacille Calmette-Guérin organisms. Bilateral loss of light perception occurred despite systemic antimy-cobacterial therapy. Histopathologic examination demonstrated nongranulomatous inflammation and acid-fast bacilli in both eyes. CONCLUSION: Delayed endogenous endophthalmitis may develop after intravesicular bacille Calmette-Guérin injection that may not respond to systemic agents. Intravitreal therapy may be indicated.

Preoperative use of tissue plasminogen activator for large submacular hemorrhage.

BACKGROUND AND OBJECTIVE: Tissue Plasminogen Activator (TPA) has been used as an adjunct in the surgical removal of submacular hemorrhage. It is usually used intraoperatively, but may not provide enough time for effective fibrinolysis, especially for a large hemorrhage. The present study was conducted to evaluate the efficiency and safety of preoperative use of TPA for large submacular hemorrhages. METHODS: Five eyes with large submacular hemorrhage secondary to age-related macular degeneration underwent subretinal injection of TPA in the office 24 hours before surgery. All hemorrhages were less than seven days old and at least 3 mm thick. RESULTS: Preoperative visual acuity ranged from counting fingers to hand motion (HM). Patient follow-up ranged from 3 months to 24 months (mean, 11 months). Final visual acuity ranged from 20/30 to HM. Four of the five eyes (80%) showed improved visual acuity after surgery and 3/5 (60%) attained visual acuity of 20/200 or better. CONCLUSION: Preoperative use of TPA for drainage of large submacular hemorrhage appears to be safe and may result in efficient clot removal. The true efficacy of TPA in the treatment of submacular hemorrhage can only be proven by a prospective randomized trial.

Progression of diabetic retinopathy after endophthalmitis.

OBJECTIVE: To determine the effect of endophthalmitis on diabetic retinopathy. DESIGN: Noncomparative case series. METHODS: The records of all consecutive patients with endophthalmitis treated between 1992 and 1997 at the Medical College of Wisconsin were retrospectively reviewed. Those patients with diabetes mellitus were analyzed. PARTICIPANTS: From 77 reviewed records, 11 patients (12 eyes; 14%) were identified as diabetics with endophthalmitis and were studied. MAIN OUTCOME MEASURES: Stage of diabetic retinopathy, time to retinopathy progression, and visual acuity. RESULTS: Mean patient age was 68 years, and mean duration of diabetes was 11.7 years. Mean patient follow-up was 17 months. Of the six cases without evidence of retinopathy before the endophthalmitis, none went on to develop retinopathy. Of six eyes with pre-existing nonproliferative retinopathy, four showed evidence of progression within 6 months of the infection. Three developed severe proliferative disease and macular edema, and one developed severe nonproliferative disease. More patients without pre-existing retinopathy achieved a final visual acuity of 20/40 or greater. CONCLUSIONS: Patients with pre-existing diabetic retinopathy may be at increased risk for rapid retinopathy progression and a poorer visual outcome after endophthalmitis. These results support the concept that inflammation may exacerbate diabetic retinopathy.