Clinical Features of Glaucoma Associated with Cytomegalovirus Corneal Endotheliitis.

Purpose: The purpose of this study was to highlight the manifestations of glaucoma associated with cytomegalovirus (CMV) corneal endotheliitis. Methods: We reviewed the 34 patients that met the diagnostic criteria for CMV endotheliitis in our hospital, with special attention to the glaucoma status, including onset of glaucoma, glaucoma in the fellow eye, visual field defects, intraocular pressure, and final outcomes. Results: Thirty-four eyes of 34 patients (mean age, 69.1 ± 13.1 years; 31 males [91.2%]) with CMV corneal endotheliitis were enrolled. Thirty-two eyes (94.1%) had a history of a glaucoma diagnosis, which had been treated for 10.0 ± 10.1 years. Glaucoma in the fellow eye was noted in 16 cases (47.1%) and a history of Posner-Schlossman syndrome was noted in 13 cases (38.2%). Visual fields measured using a Humphrey field analyzer were normal-to-early stage (MD>-6dB) in 16 eyes (47.1%) and middle-to-late stage (MD≤-6dB) in 18 eyes (52.9%). The intraocular pressure decreased from 22.4 ± 10.6 mmHg at the initial visit to 14.9 ± 7.9 mmHg after medical treatment, including 0.5% topical ganciclovir (GCV) with and without a systemic anti-CMV agent, corticosteroid eye drops, and an anti-glaucoma agent (p<0.01). During the follow-up period of 4.8 ± 3.0 years (range, 0.2-10 years), 16 eyes (47.1%) required glaucoma surgery, including filtering surgery (7 eyes) and trabeculotomy only (9 eyes). Conclusion: Our case series showed that most of the patients with CMV corneal endotheliitis had glaucoma. Although medical therapy, including 0.5% topical GCV, had efficacy in lowering the intraocular pressure, one-half of the cases required glaucoma surgery. Therefore, ophthalmologists should strive to make an earlier diagnosis of CMV corneal endotheliitis by utilizing PCR testing of aqueous humor samples to prevent sight-threatening glaucomatous damage.

Development of Cytomegalovirus Corneal Endotheliitis During Long-Term Topical Tacrolimus and Steroid Treatment for Chronic Ocular Surface Inflammatory Diseases.

PURPOSE: We report 3 cases of patients with chronic ocular surface inflammatory disease who developed cytomegalovirus (CMV) corneal endotheliitis during immunosuppressant and steroid treatment. PATIENTS AND METHODS: This is a retrospective observational study analyzing the clinical characteristics and outcomes of 3 patients with ocular surface inflammatory diseases (2 with Mooren ulcer and 1 with idiopathic scleritis) who developed CMV corneal endotheliitis. All patients developed CMV corneal endotheliitis between 8 and 14 months of starting steroid and immunosuppressant treatment, including topical 0.1% tacrolimus. Decimal visual acuity, endothelial counts, and intraocular pressure were analyzed. RESULTS: All patients received topical 0.5% ganciclovir after the diagnosis of CMV corneal endotheliitis, which improved endothelial inflammation. However, all patients developed irreversible mydriasis and required additional surgeries, including endothelial keratoplasty, cataract surgery, and glaucoma surgery. At the final follow-up (14-46 months post-CMV corneal endotheliitis onset), fair outcomes were achieved, as demonstrated by a mean decimal best-corrected visual acuity of 0.3 and a well-controlled intraocular pressure. CONCLUSIONS: Topical steroids and immunosuppressants can induce fulminant CMV corneal endotheliitis with cataract progression and irreversible mydriasis. In these cases, early diagnosis and treatment, including topical 0.5% ganciclovir, glaucoma surgery, cataract surgery, and endothelial keratoplasty, are necessary for preserving the patient's vision.

Choroidal circulation impairment during the anterior recurrence of Vogt-Koyanagi-Harada disease confirmed with indocyanine green angiography and laser speckle flowgraphy.

PURPOSE: To assess choroidal inflammation-related circulatory changes associated with the anterior recurrence of Vogt-Koyanagi-Harada (VKH) disease, using indocyanine green angiography (ICGA) and laser speckle flowgraphy (LSFG). METHODS: This retrospective case series included 17 eyes of 11 patients with VKH disease showing recurrent inflammatory findings in the anterior, but not posterior, segment (i.e. anterior recurrence). Indocyanine green angiography (ICGA) and LSFG were performed at the time of recurrence and one month after the initiation of corticosteroid therapy. The number and total area of hypofluorescent dark dots (HDDs) on ICGA were independently counted by three physicians and measured with ImageJ, respectively. Mean blur rate (MBR), a quantitative index of relative blood flow velocity, was calculated via the LSFG Analyzer software. RESULTS: Hypofluorescent dark dots (HDDs) were identified on ICGA in 13 of 17 eyes (76%) with the anterior recurrence of VKH disease. The number and total area of HDDs significantly decreased from 203 ± 101 dots to 59 ± 51 dots and from 48 789 ± 24 251 pixels to 15 664 ± 13 254 pixels, respectively. The change ratio of MBR significantly increased by 17.9 ± 16.3% after the treatment. Importantly, there was no significant association between the change ratios of HDDs and MBR. CONCLUSIONS: These findings on LSFG and ICGA clearly demonstrated subclinical involvement as well as post-treatment improvement of choroidal circulation impairment due to granulomatous inflammation in eyes with the anterior recurrence of VKH disease. The present data suggest the validity of using these two examinations, capable of detecting different circulatory changes, in the management of recurrent VKH disease.

Two cases of subfoveal choroidal neovascularization with tubulointerstitial nephritis and uveitis syndrome.

PURPOSE: Tubulointerstitial nephritis and uveitis (TINU) syndrome usually shows anterior segment intraocular inflammation, but severe posterior segment intraocular inflammation is rarely observed. We report 2 children with TINU syndrome complicated by subfoveal choroidal neovascularization (CNV). METHODS: Case reports. RESULTS: Patients were a 12-year-old girl and a 12-year-old boy diagnosed with probable TINU syndrome on the basis of typical ocular findings and high value of urinary ß2 microglobulin even though renal biopsy was not performed. The girl showed development of CNV with subretinal macular hemorrhage along with the exacerbation of anterior chamber inflammation in her left eye. Subretinal macular hemorrhage recurred frequently even with oral prednisolone; therefore, intravitreal injection of bevacizumab (IVB) was performed. After IVB, the subretinal proliferative tissue shrunk and subretinal hemorrhage has not recurred for 5 years. The boy showed subretinal hemorrhage from CNV with severe anterior chamber inflammation in his left eye. With oral prednisolone, anterior chamber inflammation and subretinal hemorrhage disappeared, but shrunken subretinal fibrosis in the macula remained. Final visual acuity was poor due to residual subretinal fibrosis in both cases. CONCLUSIONS: Tubulointerstitial nephritis and uveitis syndrome has a potential to develop CNV that leads to severe visual loss; therefore, prompt anti-inflammatory therapy is required, and IVB should be regarded as a potential choice of treatment.

Correlation between elevation of serum antinuclear antibody titer and decreased therapeutic efficacy in the treatment of Behçet's disease with infliximab.

BACKGROUND: Infliximab, an anti-TNF-α monoclonal antibody, administered to Behçet's disease (BD) patients in Japan with refractory intraocular inflammation, has shown excellent clinical results. However, some patients demonstrate a decreased response to infliximab during the course of the treatment. In the present study, we investigated the correlation between this reduced therapeutic effect and elevation of the serum antinuclear antibody (ANA) titers in patients with BD who were undergoing infliximab therapy. METHODS: Seventeen patients (14 males and three females) with uveitis in BD who were undergoing treatment with infliximab for 2 years or longer were enrolled. Their blood test results and clinical histories were obtained from medical records. RESULTS: One patient (5.9%) was ANA-positive prior to the initiation of infliximab, and 11 patients (64.7%) developed positive ANA during the therapy. The appearance of ANA was observed 6 months after the initiation of the infliximab therapy, and its titers gradually increased. None of the patients showed lupus symptoms. Five patients (29.4%) have suffered from ocular inflammatory attacks since the sixth month from the initiation of infliximab treatment and all of them were ANA-positive. In contrast, four patients (23.5%) who were ANA-negative experienced no ocular attacks during the follow-up period. CONCLUSIONS: Here we report the positive conversion and subsequent elevation of serum ANA titers in some patients with BD after the initiation of infliximab therapy. Since all recurrences of uveitis were shown only in the ANA-positive patients, serum ANA titer may be a helpful biomarker for predicting the recurrence of ocular attacks in BD patients treated with anti-TNF-α antibody therapies.

The effects of Ginkgo biloba extract on lipopolysaccharide-induced inflammation in vitro and in vivo.

PURPOSE: Ginkgo biloba extract (GBE) contains many different flavone glycosides and terpenoides. Several previous studies have demonstrated that GBE exhibits a wide variety of biological activities, including an antioxidant action, on which we focused our attention. The aim of the present study was to investigate the efficacy of GBE on endotoxin induced uveitis in rats. The anti-inflammatory potency of GBE in vivo was compared with that of prednisolone. In addition, we also investigated nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and the expression of iNOS in a mouse macrophage cell line (RAW 264.7) treated with GBE in vitro to clarify the anti-inflammatory effect. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, either 1, 10 or 100 microg of GBE were injected intravenously. 24hr later, the aqueous humor was collected from both eyes, and the number of infiltrating cells, protein concentration and NO level in the aqueous humor was determined. The RAW 264.7 cells were pretreated with various concentrations of GBE for 24hr and subsequently incubated with LPS for 24hr. Levels of NO, PGE2 and TNF-alpha were determined by enzyme-linked immunosorbent assay. The expression of iNOS protein was analyzed by Western blotting method. RESULTS: GBE treatment in vivo decreased the concentrations of protein and NO in the aqueous humor of EIU rats. The anti-inflammatory effect of 1 mg GBE was as strong as that of same dose prednisolone. It also significantly reduced the concentration of PGE2, TNF-alpha and NO production in the medium of RAW 264.7 cells compared to that of the LPS group in vitro. The expression of iNOS protein in the 1000 microg ml(-1) of GBE treated cells decreased significantly. CONCLUSION: The present results indicate GBE suppresses the inflammation of EIU by blocking the iNOS protein expression and its anti-inflammatory effect on eye is comparable with the effect of prednisolone used in similar doses.