The 'Insertion/Deletion' Polymorphism, rs4340 and Diabetes Risk: A Pilot Study from a Hospital Cohort.

The insertion/deletion, I/D polymorphism, in the gene encoding Angiotensin Converting Enzyme, ACE is a popular genetic marker for cardiovascular disease, CVD. With alarming rise in diabetes, the risk of CVD among Indian subjects is further enhanced. The present study explored the role of ACE I/D polymorphism, rs4340 as a genetic marker and its association with diabetes. Genomic DNA, isolated from a cohort of 410 urban subjects attending our hospital, was genotyped using polymerase chain reaction followed by electrophoresis. Among the subjects, 84 had type-2 diabetes and 68 had hypertension while 258 were free from these risk factors. Majority (57/84) of diabetic subjects were also suffering from hypertension. Genotype frequencies of ACE I/D polymorphism, of diabetic (84) patients were not different from that of non-diabetic subjects (258). In sharp contrast, we found significant differences, in genotype frequencies of women with diabetes (n = 38) compared to non-diabetic women (70). Diabetic women had significantly higher prevalence of the high risk 'D' allele. Analysis of odds ratio, OR revealed that women with 'D/D' genotype, exhibited threefold risk (OR 3.12, 95% CI 1.21-8.05; p = 0.018) of diabetes, in the recessive model (D/D vs I/I + I/D). Further when we analysed Odds ratio of diabetic women (8) who were free from hypertension, the results revealed even a greater, 6- fold (OR 6.0, 95% CI 1.29-27.96, p = 0.027) risk of diabetes for D/D homozygous women (D/D vs I/I + I/D). These results suggest 'sex-specific' association of ACE 'I/D' polymorphism, with type-2 diabetes, affecting women while there was no influence observed among men. In view of the increased cardiovascular mortality among Indians, data from our pilot study if confirmed in a larger cohort, could add value to our future intervention efforts.

Moxifloxacin Concentration and Proteomic Analysis of Aqueous Humor in Human Uveitis Associated with Oral Moxifloxacin Therapy.

PURPOSE: The aim was to report the aqueous humor moxifloxacin concentration and proteome profile of an individual with bilateral uveitis-like syndrome with pigment dispersion. METHODS: Multiple reactions monitoring mass spectrometry quantified the aqueous concentration of moxifloxacin in the affected individual. Shotgun proteomic analysis performed via liquid chromatography tandem mass spectrometry (LC-MS/MS) defined the protein profile in the affected individual and unaffected control samples. RESULTS: Moxifloxacin was present at higher than expected levels in aqueous humor 18 days following oral administration. One-third of the proteins were identified by significantly lower spectral counts in the aqueous of the individual with moxifloxacin associated uveitis compared to the unaffected control. CONCLUSION: Moxifloxacin was detected in aqueous humor 18 days following the completion of oral administration. These results suggest that moxifloxacin toxicity may be responsible for the uveitis-like syndrome with pigment dispersion syndrome induced by moxifloxacin therapy.

Scleritis associated with relapsing polychondritis.

AIMS: To evaluate ocular disease characteristics and successful therapeutic regimens in patients with scleritis associated with relapsing polychondritis (RP). To compare these features with those seen in patients with scleritis associated with other systemic immune-mediated diseases (SIMD). METHODS: Electronic health records of 13 scleritis patients associated with RP were analysed and compared with those of 113 scleritis patients associated with other SIMD seen at two tertiary referral centres. RESULTS: Scleritis in patients with RP was often bilateral (92.3%), diffuse (76.9%), recurrent (84.6%), sometimes with decreased vision (46.2%), anterior uveitis (38.5%), peripheral keratitis (15.4%) and ocular hypertension (30.8%). Patients with scleritis associated with RP more often had bilateral scleritis (p=0.001), necrotising scleritis (23.1%; p=0.02), recurrences (p=0.001) and decreased vision (three of the six with legal blindness; p=0.012), as compared with patients who had scleritis associated with other SIMD. Nine patients (69.2%) had one or more SIMD other than RP, including systemic vasculitis (4) or other autoimmune disease (8); they antedated RP by 9 years (range 2-21 years). Successful therapy included cyclophosphamide (5), methotrexate (3), azathioprine (3), mycophenolate mofetil (2), infliximab (2) and adalimumab (1). CONCLUSIONS: Scleritis may be the first manifestation whose study leads to the diagnosis of RP. Scleritis associated with RP is more often bilateral, necrotising, recurrent and associated with decrease of vision than scleritis associated with other SIMD. About 69.2% of patients will have an additional SIMD disorder. Scleritis associated with RP most often will require immunomodulatory therapy. Occasionally, scleritis with RP may appear while using antitumor necrosis factor α agents.

Scleritis in patients with granulomatosis with polyangiitis (Wegener).

AIMS: To describe and compare clinical features, complications and outcomes in patients with granulomatosis with polyangiitis (GPA)-associated scleritis with those seen in idiopathic and other autoimmune-associated scleritis, and to further describe the features that may serve as an indicator of life-threatening systemic disease. METHODS: We retrospectively reviewed electronic health records of all patients with scleritis seen at two tertiary care centres. Of 500 patients, 14 had GPA-associated scleritis and were included in this analysis. Measures included were age, gender, laterality, visual acuity and underlying systemic or ocular diseases. Clinical features (location, pain, inflammation) and ocular complications of these patients (decrease of vision, concomitant anterior uveitis and ocular hypertension) were studied and correlated. RESULTS: Fourteen of 500 patients with scleritis were GPA associated. Most of the patients with GPA-associated scleritis presented with sudden onset, bilateral, diffuse anterior scleral inflammation, with moderate-or-severe pain. Vision loss was not significantly different, and pain was more severe in these patients than in those with idiopathic scleritis. When compared with patients with other underlying autoimmune diseases, there were no significant differences found in epidemiological or clinical signs. Necrotising scleritis and corneal involvement were more commonly observed in GPA than in idiopathic scleritis and other autoimmune diseases and are often the presenting feature of the disease. CONCLUSIONS: The presence of necrotising changes or corneal involvement in the setting of scleral inflammation is highly suggestive of an underlying systemic vasculitis, of which GPA is the most common. These features should alert the doctor/optometrist and prompt a thorough diagnostic approach and an aggressive treatment given that it could reveal a life-threatening disease.

Clinical features and presentation of posterior scleritis: a report of 31 cases.

PURPOSE: To describe clinical features, ocular complications, and visual outcomes of patients with posterior scleritis. METHODS: Clinical characteristics of a subset of 31 patients with posterior scleritis were studied and compared with 469 patients with anterior scleritis. RESULTS: Of 500 patients, 31 (6.2%) had posterior scleritis. Most patients presented with subacute (80.6%), unilateral (61.3%) scleral inflammation. Pain was moderate to severe in 54.8% of patients. Concomitant anterior scleritis was observed during follow-up in 77.4% of patients and in all patients with moderate to severe pain. Patients with posterior scleritis were significantly younger (43.6 vs. 54.4 years, p < 0.001) and had significantly higher decrease of vision (29.0 vs. 14.9%, p = 0.027) than those with isolated anterior scleritis. CONCLUSIONS: Posterior scleritis must be considered in patients with decrease of vision, mild to severe pain, optic disc edema, and/or posterior uveitis. Moderate to severe pain may be associated with poorer visual outcome.

Clinical features and presentation of infectious scleritis from herpes viruses: a report of 35 cases.

PURPOSE: To describe clinical features and presentation of infectious scleritis resulting from herpes viruses. DESIGN: Retrospective case series. PARTICIPANTS: Thirty-five patients out of 500 with scleritis. METHODS: We reviewed the electronic health records of 500 patients with scleritis, 35 of whom were diagnosed with herpes virus infection, seen at 2 tertiary referral centers. We studied the clinical features and ocular complications of this subset of patient with scleritis. MAIN OUTCOME MEASURES: Correlation between classification, severity, and symptoms (i.e., pain) and diagnosis of herpetic-associated scleritis. Vision loss, presence of associated uveitis, keratitis, glaucoma, or systemic disease were documented over the follow-up period. Other outcome measures included epidemiologic data: age, gender, laterality, visual acuity, duration of symptoms, and underlying systemic or ocular diseases. RESULTS: Of 500 patients with scleritis, 47 (9.4%) had an underlying infectious cause. Thirty-five (74.4%) of these were diagnosed with herpes virus infection, 5 (10.6%) with tuberculosis, and the remaining 7 (14.8%) with other infectious disease. Patients with herpes-associated scleritis were analyzed as a group and then compared with those with idiopathic scleritis. Most patients with herpetic scleritis presented with acute (85.7%) and unilateral (80%) scleral inflammation. Pain was moderate or severe in 68.6% of the patients. The most common type of scleritis was diffuse anterior in 80% (n = 28), followed by nodular anterior 11.4% (n = 4), and necrotizing in 8.6% (n = 3). Necrotizing anterior scleritis was more commonly seen in patients with herpetic scleritis versus patients with idiopathic disease (8.6% vs 1.2%; P<0.05). Unilaterality was also more common in herpetic scleritis (80%) than in idiopathic disease (56.7%; P<0.05). Vision loss was significantly greater in herpetic than idiopathic scleritis (34.3% vs 11.5%; P<0.001). CONCLUSIONS: The association between scleritis and infectious disease may be higher than previously reported by other series. Herpes viruses account for 7% of all scleritis cases and its diagnosis may be challenging when there is not a classically diagnostic clinical picture. We present the observed clinical features of herpetic scleritis and describe the clinical differences at presentation between patients with idiopathic scleritis and those with herpes infection.

Clinical characteristics of a large cohort of patients with scleritis and episcleritis.

OBJECTIVE: To evaluate the demographic characteristics, clinical features, ocular complications, and disease associations of patients with scleritis and episcleritis; as well as to delineate the risk factors for decreased vision in patients with scleritis. DESIGN: Retrospective case series. PARTICIPANTS: Five hundred patients with scleritis and 85 patients with episcleritis. METHODS: The electronic health records of 500 patients with scleritis and 85 patients with episcleritis seen at 2 tertiary referral centers were reviewed and their clinical features were studied. MAIN OUTCOME MEASURES: Clinical features (pain, scleral inflammation), ocular complications (decrease in vision, anterior uveitis, peripheral ulcerative keratitis, ocular hypertension), and disease associations. RESULTS: In a series of 585 patients, 500 patients had scleritis (85.5%) and 85 patients had episcleritis (14.2%). Ocular complications were more frequent overall in patients with scleritis versus in those with episcleritis (45.0% vs. 19.0%), including decrease in vision (15.8% vs. 2.3%), anterior uveitis (26.4% vs. 16.5%), peripheral ulcerative keratitis (7.4% vs. 0%), and ocular hypertension (14.2% vs. 3.5%; P<0.0001 for each). Disease association was observed in 35.8% of patients with scleritis versus 27.1% of episcleritis patients, including connective tissue or vasculitic diseases in 24.8% versus 15.3%, respectively. Scleritis preceded systemic disease diagnosis in 38.7% of patients. Ocular complications (90.0%) and disease association (80.0%) occurred most often in patients with necrotizing scleritis (P<0.0001 for each). Risk factors for decrease in vision in patients with scleritis included necrotizing scleritis (odds ratio [OR], 6.63; P<0.001), posterior scleritis (OR, 2.33; P = 0.042), degree of scleral inflammation of more than 2+ (range, 0-4+; OR, 3.60; P<0.001), anterior uveitis (OR, 1.78; P = 0.033), ocular hypertension (OR, 3.19; P<0.001), and associated disease (OR, 2.66; P<0.001), mainly infectious (OR, 4.44; P<0.001). CONCLUSIONS: Scleritis is associated more often with ocular complications than episcleritis, and necrotizing scleritis is the type of scleritis most often associated with ocular complications and disease association. Risk factors for decrease in vision in patients with scleritis include necrotizing scleritis, posterior scleritis, scleral inflammation of more than 2+, anterior uveitis, ocular hypertension, and associated infectious disease. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Scleritis therapy.

OBJECTIVE: To delineate factors associated with a successful response to treatment in patients with various manifestations of scleritis. DESIGN: Retrospective case series. PARTICIPANTS: A total of 392 patients with noninfectious anterior scleritis. METHODS: We reviewed the electronic health records of 392 patients with noninfectious anterior scleritis seen at 2 tertiary referral centers and studied the factors associated with successful treatment. MAIN OUTCOME MEASURES: Patient characteristics (age, sex); ocular disease characteristics (laterality, type of scleritis, degree of scleral inflammation, ocular complications, delay in presentation, and follow-up period), systemic disease association (associated disease, potentially lethal associated disease); and anti-inflammatory and immunosuppressive medications were studied in patients with scleritis. Successful treatment response to nonsteroidal anti-inflammatory drugs (NSAIDs), steroidal anti-inflammatory drugs (SAIDs), immunosuppressive therapy drugs (immunomodulatory therapy [IMT]), or biologic response modifiers (BRMs) was assessed. RESULTS: Treatment of 392 patients with noninfectious anterior scleritis included NSAIDs in 144 (36.7%), SAIDs in 29 (7.4%), IMT in 149 (38.0%), BRMs in 56 (14.3%), and none (N = 14). Successful response to treatment with NSAIDs was associated with idiopathic diffuse or nodular scleritis with a low degree of scleral inflammation (≤ 2+) (odds ratio [OR] = 2.89, P < 0.001) and with idiopathic diffuse or nodular scleritis without ocular complications (OR = 3.13, P < 0.001). Successful treatment with SAIDs was associated with idiopathic diffuse or nodular scleritis with a high degree of scleral inflammation (>2+) (OR = 4.70, P = 0.001). Successful treatment with IMT was associated with diffuse or nodular scleritis with associated systemic disease (OR = 1.57, P = 0.047), mainly potentially lethal (OR = 17.41, P=0.007), and necrotizing scleritis (OR = 4.73, P = 0.026). Successful treatment with BRMs was associated with diffuse or nodular scleritis with associated systemic disease (OR = 3.15, P < 0.001). This study did not require institutional review board approval because the information does not contain any subject identifiers. CONCLUSIONS: Patients with idiopathic diffuse or nodular scleritis with a low degree of scleral inflammation or without ocular complications may respond to NSAIDs. Patients with idiopathic diffuse or nodular scleritis with a high degree of scleral inflammation may respond to SAIDs. Patients with diffuse or nodular scleritis with associated systemic disease may respond to IMT or BRMs. Patients with necrotizing scleritis may respond to IMT, mainly alkylating agents. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Infliximab for the treatment of refractory scleritis.

BACKGROUND Scleritis is a potentially blinding inflammatory disorder. Standard care consists of systemic corticosteroids and immunosuppresants. The authors describe a series of 10 patients suffering from scleritis treated with the TNF inhibitor infliximab because this scleritis was refractory to standard therapy. METHODS The authors reviewed the medical records of patients with scleritis at the Massachusetts Eye Research and Surgery Institution, treated with infliximab. All cases had non-infectious scleritis refractory to traditional immunomodulatory therapy and received 5 mg/kg of infliximab at 4-8-weekly intervals. The main outcome measures evaluated were clinical response, reduction in concomitant immunomodulatory therapy and adverse effects. Inflammation control and visual acuity were assessed using life-table methods. RESULTS A favourable clinical response to infliximab was seen in 100% of the patients, with six (60%) of them achieving remission and cessation of concomitant immunosuppression. A clinical response to infliximab therapy occurred within 13.24 weeks on average. Based on clinical response, the authors found that repeat monthly infusions were required to maintain remission. One (10%) patient developed a lupus-like reaction necessitating discontinuation of infliximab. CONCLUSION Infliximab may be considered in the treatment of non-infectious scleritis refractory to other treatment.

Mycophenolate mofetil therapy for sarcoidosis-associated uveitis.

PURPOSE: To evaluate the control of ocular inflammation and the steroid sparing effect in patients with sarcoidosis-associated uveitis treated with mycophenolate mofetil (MMF). METHODS: Retrospective case series. All patients with a diagnosis of sarcoidosis-associated uveitis that were treated with MMF between 2005 and 2007 were identified. The dose and duration of MMF therapy and side effects were recorded. RESULTS: Seven patients (14 eyes) with sarcoidosis-associated uveitis were treated with MMF. The mean duration of treatment was 10 +/- 4.7 months and the average time to control uveitis was 6.7 weeks. The flare-up rate was 51.5 per 100 person-years follow-up. The best-corrected mean logMAR VA revealed improvement in all 14 eyes. The efficacy of MMF in keeping disease activity under control was maintained in 6 patients. CONCLUSION: These data suggest that MMF is effective in controlling sarcoidosis-related ocular inflammation, has a corticosteroid sparing effect and a manageable side-effect profile.

Intravitreal bevacizumab for uveitic choroidal neovascularization.

PURPOSE: To report 5 cases of inflammatory choroidal neovascularization (CNV) that were treated with intravitreal bevacizumab. METHODS: Six eyes of 5 patients with uveitic CNV were treated with 2.5 mg/0.1 mL of intravitreal bevacizumab. Main outcome measures were the changes in BCVA and reduction in the size of the CNV. RESULTS: The mean follow-up time was 15.3 months. The mean intravitreal injections administered were 2.7. All patients showed a reduction in the size of the CNV with improvement in BCVA in 60% of cases at the last follow-up. CONCLUSION: Intravitreal bevacizumab may provide an additional strategy in the management of inflammatory CNV.

Intravenous daclizumab for recalcitrant ocular inflammatory disease.

BACKGROUND: To evaluate outcomes of patients with recalcitrant ocular inflammation treated with intravenous daclizumab. METHODS: Retrospective case-series. Seventeen patients (33 eyes) with ocular inflammation who had failed several previous systemic immunomodulatory therapies were included in this study. Daclizumab was infused intravenously at a dose of 1 mg per kilogram every 2 weeks. The dose and intervals were adjusted according to control of inflammation off systemic and/or topical corticosteroid therapy. Control of ocular inflammation without corticosteroid therapy was the primary efficacy end point. RESULTS: The mean patient age at the commencement of daclizumab therapy was 34.8(range 8-64 years). Three patients were less than 16 years of age at the initiation of therapy. The duration of drug use was 23.6 +/- 15.7 months (range 8-68 months), and the time to control inflammation was 9.8 +/- 11.3 weeks, which was achieved in 15 patients (88.2%). Flare-up rate was 44 per 100 person-years follow-up. Fifteen of 33 eyes (45%) had an improvement in the visual acuity, 13 eyes (39.3%) had stable acuities, and five eyes (15%) had a worsening of their acuities. Two patients (14%) exhibited worsening of ocular inflammation, and were declared as treatment failures. Side effects associated with daclizumab included nausea, fatigue and muscle aches. CONCLUSION: Daclizumab is effective in controlling inflammation in patients with stubborn non-infectious ocular inflammation. It has a corticosteroid-sparing effect, can be used as long-term therapy in children and adults, and is capable of inducing durable remission.

Flare-up rates with bimatoprost therapy in uveitic glaucoma.

PURPOSE: To evaluate the rate of flares in patients with uveitic glaucoma treated with topical bimatoprost and to assess its effect on intraocular pressure (IOP) in this subset of patients. DESIGN: Retrospective case series. METHODS: All patients seen at one subspecialty uveitis practice with history of uveitic glaucoma treated with topical bimatoprost were identified and the data collected, which included onset, type, duration of uveitis, onset of secondary glaucoma, and previous therapies for glaucoma. The time of onset of bimatoprost therapy, the IOP, and flare-up rate before and after initiation of treatment with bimatoprost were recorded at one week and one, three, and six months of follow-up. RESULTS: Of the 42 patients (59 eyes) identified, 12 patients had used other topical lipid agents, which were replaced by bimatoprost. Twenty-three patients had not used any lipid agents and bimatoprost was added to their existing antiglaucoma regimen. Seven patients were newly diagnosed with uveitic glaucoma and were commenced with topical bimatoprost. The rate of uveitis flares while on other antiglaucoma therapy was 52 per 100 person-years follow-up, while on bimatoprost therapy it was 32.4 per 100 person-years follow-up (P = .206). The mean IOP prior to bimatoprost therapy was 27 +/- 13.2 mm Hg and after initiation of topical bimatoprost was 15 +/- 5.5 mm Hg at the end of six months (P = .0008). CONCLUSION: These data suggest that bimatoprost is an effective IOP-lowering agent in patients with uveitic glaucoma in whom the uveitis is controlled on immunomodulatory therapy, and it does not increase the rate of flares of uveitis in these patients.

Subconjunctival bevacizumab for corneal neovascularization.

PURPOSE: To describe whether subconjunctival bevacizumab decreases corneal neovascularization in patients with ocular surface inflammatory diseases. METHODS: The study is a retrospective case series that includes 8 eyes of 7 patients with corneal neovascularization. Patients received 1-3 injections of 2.5 mg subconjunctival bevacizumab. Morphologic changes were assessed clinically by the same investigator at each visit. RESULTS: Subconjunctival bevacizumab was well-tolerated without obvious corneal side effects. All 8 eyes of the 7 patients showed a reduction in the neovascularized area. CONCLUSIONS: Subconjunctival bevacizumab may provide an additional strategy in improving vision or improving success of corneal grafts in these patients.