Plasmapheresis as a viable treatment option for scleritis.

Purpose: We describe a case and our experience with using plasmapheresis as a treatment for scleritis. Observations: Treating relapsing autoimmune scleritis can be challenging when it inadequately responds to traditional therapy. Our patient could not receive non-steroidal anti-inflammatory therapy for her scleritis due to recent gastrointestinal surgery and previously failed multiple steroid sparing treatments due to intolerance. There was good initial control with high dose oral prednisone, however, the steroid could not be tapered to a safe dosage (<10 mg per day) without relapse. Therefore, we opted to treat our patient with plasmapheresis. Conclusions and Importance: After undergoing plasmapheresis, our patient experienced total resolution of symptoms with corresponding clinical resolution of scleritis. Plasmapheresis derives great benefit by filtering circulating immune complexes. Although rarely used, plasmapheresis can be effective in treating non-infectious scleritis.

Endophthalmitis after pars plana vitrectomy with reused single-use devices: a 13-year retrospective study.

BACKGROUND: To describe the incidence, clinical characteristics, and treatment outcomes of endophthalmitis after pars plana vitrectomy (PPV) with recycled single-use devices. The recommended sterilization process as well as safety measures are discussed. METHODS: Medical charts of patients who developed endophthalmitis after PPV were retrospectively reviewed and reported in a descriptive manner. Cases undergoing PPV for preexisting endophthalmitis or open globe injury were excluded. Data collection included patient demographics, operative details, ocular findings, microbiological profiles, treatment modalities, and visual outcomes. RESULTS: Over the past thirteen years, a total of 12,989 pars plana vitrectomy operations were included. In total, 13 eyes of 13 cases (0.10%) experienced endophthalmitis after vitrectomy. These occurred in 3 cases (0.11%) using 20-gauge vitrectomy compared to 8 cases (0.09%) using 23-gauge vitrectomy and 2 cases (0.18%) using 25-gauge vitrectomy. There were no statistically significant differences between the 20-gauge and microincisional vitrectomy surgery (MIVS) group (P = 0.64), and the 23- and 25-gauge approach (P = 0.34). Causative pathogens were positive by culture in 5 cases (45%): 3 g-positive cases, 1 g-negative case, and 1 fungus case. CONCLUSIONS: The rate of endophthalmitis in patients who underwent 23-gauge PPV was comparable to those who underwent 25-gauge PPV. With our standardized protocol for instrument sterilization, endophthalmitis rates in those undergoing PPV using recycled single-use instruments were within the range of previously published results in which vitrectomy tools were disposed of after one use.

Analysis of Three-Dimensional Choroidal Volume with Enhanced Depth Imaging Findings in Patients with Recurrent Vogt-Koyanagi-Harada Disease.

Purpose: To demonstrate changes in three-dimensional choroidal volume with enhanced depth imaging optical coherence tomography (EDI-OCT) in patients with recurrent stage of Vogt-Koyanagi-Harada disease (VKH).Materials and Methods: This prospective comparative case series included 9 patients with recurrent VKH, 10 patients with quiet VKH, and 15 healthy controls after sample size was calculated. All VKH cases with recurrences underwent raster scanning with EDI-OCT at active and inactive stages of the disease.Results: All choroidal parameters in the active stage significantly reduced when the inflammation subsided: total choroidal volume (P = .02), central choroidal volume (P = .01), central choroidal thickness (P = .03). The changes in central choroidal volume over the resolution phase were more pronounced than the changes in central choroidal thickness in 56% of cases. Two cases presenting with only subclinical posterior segment recurrence had their choroidal parameters recovered after prompt treatment.Conclusions: In the recurrent stage of VKH, alteration in choroidal volume was evident by EDI-OCT even in an absence of anterior segment inflammation. Central choroidal volume may serve as a biomarker for detecting choroidal morphological change.

Poor prognostic factors in post-traumatic endophthalmitis following open globe injury.

AIM: To demonstrate prognostic factors for poor visual outcome in patients with post-traumatic endophthalmitis (PTE) following open globe injury. METHODS: A retrospective study was conducted on 66 patients (66 eyes) with PTE following open globe injury from 2005 to 2015. Potential factors accounting for good and poor visual outcome were statistically analyzed by Chi-square test and Logistic regression model. RESULTS: In 66 cases, 39 cases (59%) had a poor visual outcome. Univariate and multivariate Logistic regression analysis identified retained intraocular foreign body (IOFB) as the only factor significantly associated with poor visual outcome [adjusted odds ratio, 4.62; 95% confidence interval (1.04-20.53); P=0.04]. The most common causative agents were gram-positive organisms (83%), of which Bacillus cereus (33%), was the most common pathogen. All cases received intravitreal antibiotic injections. Oral ciprofloxacin was the most used systemic antibiotic (33%). Pars plana vitrectomy was performed in 83% (55/66) of cases. At 6mo follow-up, mean BCVA was 1.74±0.72 logMAR units. CONCLUSION: In patients with PTE following open globe injury, the only predictor of poor visual outcome is the presence of IOFB. Bacillus cereus is the most isolated microorganism.

Homonymous Horizontal Sectoranopia Caused by an Occipital Lobe Infarct.

Homonymous horizontal sectoranopia is a rare visual field defect that characteristically occurs after damage to the lateral geniculate nucleus (LGN). While there are many reports of homonymous horizontal sectoranopia resulting from LGN damage, there are very few reports of homonymous horizontal sectoranopia resulting from damage to other areas of the brain. We present a unique case of a patient with a homonymous horizontal sectoranopia with an occipital lobe infarct. Visual field and radiologic findings are presented. To our knowledge, this is one of the few reported cases of homonymous horizontal sectoranopia resulting from an infarct to the occipital lobe.

VITREOUS TREPONEMAL ANTIBODY AS A SUPPLEMENTARY TEST TO SEROLOGY FOR THE CONFIRMATION OF SYPHILITIC CHORIORETINITIS.

PURPOSE: To report the novel application of nontreponemal and treponemal antibody to confirm diagnosis of ocular syphilis from vitreous samples. METHODS: Two distinct case reports emphasizing the importance of confirmatory vitreous treponemal antibody. Multimodal imaging of patients was also applied. RESULTS: We report two distinct cases with positive serum treponemal antibody but opposing vitreous treponemal antibody results. One case with a positive vitreous test responded well to antisyphilitic treatment. By contrast, a case with a negative vitreous result was changed to serpiginous choroiditis, eventually cured by immunomodulatory treatment. CONCLUSION: Intraocular fluid analysis of nontreponemal and treponemal antibody may play an important role in ruling out suspected ocular syphilis in settings without a polymerase chain reaction facility, especially immunocompromised patients who are at risk of multiple infections. Further studies are needed to establish the sensitivity and specificity of nontreponemal and treponemal antibody test on vitreous samples.

PD-1+ melanocortin receptor dependent-Treg cells prevent autoimmune disease.

Experimental autoimmune uveoretinitis (EAU) is a mouse model of human autoimmune uveitis marked by ocular autoantigen-specific regulatory immunity in the spleen. The melanocortin 5 receptor (MC5r) and adenosine 2 A receptor (A2Ar) are required for induction of post-EAU regulatory T cells (Tregs) which provide resistance to EAU. We show that blocking the PD-1/PD-L1 pathway prevented suppression of EAU by post-EAU Tregs. A2Ar induction of PD-1+FoxP3+ Tregs in uveitis patients was similar compared to healthy controls, but was significantly reduced with melanocortin stimulation. Further, lower body mass index correlated with responsiveness to stimulation of this pathway. These observations indicate an importance of the PD-1/PD-L1 pathway to provide resistance to relapsing uveitis and shows a reduced capacity of uveitis patients to induce Tregs when stimulated through melanocortin receptors, but that it is possible to bypass this part of the pathway through direct stimulation of A2Ar.

Risk factors for endophthalmitis after cataract surgery in diabetic patients: a case control study.

AIM: To identify risk factors associated with post-cataract surgery endophthalmitis (PCE) in type 2 diabetic patients. METHODS: A hospital-based retrospective case-control study was conducted on 194 type 2 diabetic patients undergoing cataract surgery in Rajavithi Hospital from January 2007 to December 2015. Fifteen patients with PCE were included as the case group and 179 patients without PCE were included as the control group. Potential factors associated with PCE among both groups including demographics, pre-operative characteristics, surgical settings and complications, were statistically analyzed using Chi-square testing and a logistic regression model. RESULTS: Within the case group, 53% were females and the median age was 68y. Univariate analysis of pre-operative characteristics, surgical settings and complications revealed that recent pre-operative fasting plasma glucose, insulin therapy, presence of diabetic retinopathy, and severe non-proliferative or proliferative diabetic retinopathy were significantly associated with PCE. In a multivariate analysis adjusting for blood glucose level, insulin treatment was the only significant factor associated with an increased risk of PCE (OR 3.9, 95%CI 1.0-15.0, P=0.04) compared to patients without insulin treatment. The most common causative organisms were gram-positive bacteria (89%). Staphylococcus species represented the most common group (67%). Median best corrected visual acuity at 1-month and 3-month follow-up was equal at 0.7 logMAR (20/100). CONCLUSION: The authors identify insulin treatment as the only risk factor associated with endophthalmitis after cataract surgery in type 2 diabetic patients. Further studies with serum levels of pre-operative glycated hemoglobin (HbA1c) and post-operative fasting plasma glucose level are essential to truly demonstrate the role of peri-operative glycemic markers as a risk factor for PCE.

Endogenous Cryptococcal Endophthalmitis in Immunocompetent Host: Case Report and Review of Multimodal Imaging Findings and Treatment.

PURPOSE: To describe a case of bilateral endogenous cryptococcal endophthalmitis in an immunocompetent host and to review adjunctive ophthalmic imaging patterns and treatment. METHODS: A retrospective case report. RESULTS: A 45-year-old female patient with two distinct presentations of endogenous cryptococcal endophthalmitis in each eye presented initially with progressive blurred vision in the left eye, beginning more than 10 years after a craniotomy with ventriculoperitoneal shunt. Complete ophthalmic imaging was conducted and compared with data from previous literature. Administration of amphotericin-B had poorly responded; however, consolidation of fluconazole resulted in disease stabilization. CONCLUSIONS: Bilateral intraocular cryptococcal infection can present with two distinct patterns of posterior segment findings. A review of ophthalmic imaging patterns found consistency in some characteristics of A-scan ultrasonogram and fundus fluorescein angiogram. Besides conventional treatment, voriconazole is likely to play an important role in the management of cryptococcal endophthalmitis.

Culture-Positive Endogenous Endophthalmitis: An Eleven-Year Retrospective Study in the Central Region of Thailand.

PURPOSE: To report the characteristics of infection and prognostic factors of endogenous endophthalmitis (EE) over an 11-year period. METHODS: The clinical records of 41 eyes of 36 patients diagnosed with culture-proven EE at the Rajavithi Hospital were retrospectively reviewed. RESULTS: Median age at presentation was 58 years. Liver abscess (19%) and urinary tract infections (19%) were the most common sources of infection. The most common causative agents were gram-negative organisms (48%). The most commonly isolated microorganism was Klebsiella pneumoniae (26.8%). Worse initial visual acuity and severe intraocular inflammation at first presentation were equally associated with poor visual outcome in the multivariate model (adjusted odds ratio, 20.32; 95% confidence interval [1.12-357.45]; P = 0.040). CONCLUSIONS: Endogenous endophthalmitis usually has a poor visual prognosis. Liver abscess and urinary tract infections are common primary sites of infection. Poor initial visual acuity and severe intraocular inflammation at the initial presentation are predictors of poor visual outcome.

Birdshot Retinochoroidopathy: Differences in Clinical Characteristics between Patients with Early and Late Age of Onset.

PURPOSE: To describe differences in the clinical characteristics of birdshot retinochoroidopathy (BSRC) patients diagnosed early and later in life. METHODS: This is a retrospective cohort study. Age was primarily analyzed and 50 years of age at diagnosis was selected as a cut-off point. RESULTS: A total of 144 patients (288 eyes) were included; 68 with early-onset and 76 with late-onset BSRC. The younger group had a statistically significant higher rate of more severe iritis (p = 0.04); an average number of non-steroidal immunosuppressants and biologic agents (NSIB) (p = 0.04); and a prolonged time to initiation of NSIB (p = 0.01). There were only four patients (3%) who had >0.5+ cells in the anterior chamber. CONCLUSIONS: Patients with early-onset BSRC carried a higher risk for anterior segment inflammation, had a more prolonged delay to initiation of treatment with NSIB, and required a greater number of NSIBs to achieve remission.

The Ex-PRESS Glaucoma Filtration Device Implantation in Uveitic Glaucoma.

PURPOSE: To evaluate the outcomes of the Ex-PRESS Filtration Device in patients with uveitic glaucoma. METHODS: We reviewed 23 eyes, comparing control simple glaucoma patients (n = 11) to uveitic glaucoma patients (n = 12). Intraocular pressure (IOP) and glaucoma medications at the preoperative examination were compared with those at the 6-month and 10-14-month postoperative examination. Surgical success was defined as ≥25% decrease in intraocular pressure without hypotony, and/or decrease in glaucoma medications at 6 months follow-up. RESULTS: Statistically significant reduction in mean IOP from preoperative levels occurred in both groups at 6 months follow-up (p<0.0001) and 10-14 months follow-up (p = 0.0007) and in the mean number of medications in the uveitic glaucoma (UG) group (p = 0.0313). CONCLUSIONS: Surgical success was seen in 10 eyes in the control group (90.9%) and nine eyes (75%) in the UG group (p = 0.314). Ex-PRESS implantation is an effective surgical intervention for the management of uveitic glaucoma.

MC5r and A2Ar Deficiencies During Experimental Autoimmune Uveitis Identifies Distinct T cell Polarization Programs and a Biphasic Regulatory Response.

Autoantigen-specific regulatory immunity emerges in the spleen of mice recovering from experimental autoimmune uveitis (EAU), a murine model for human autoimmune uveoretinitis. This regulatory immunity provides induced tolerance to ocular autoantigen, and requires melanocortin 5 receptor (MC5r) expression on antigen presenting cells with adenosine 2 A receptor (A2Ar) expression on T cells. During EAU it is not well understood what roles MC5r and A2Ar have on promoting regulatory immunity. Cytokine profile analysis during EAU revealed MC5r and A2Ar each mediate distinct T cell responses, and are responsible for a functional regulatory immune response in the spleen. A2Ar stimulation at EAU onset did not augment this regulatory response, nor bypass the MC5r requirement to induce regulatory immunity. The importance of this pathway in human autoimmune uveitis was assayed. PBMC from uveitis patients were assayed for MC5r expression on monocytes and A2Ar on T cells, and comparison between uveitis patients and healthy controls had no significant difference. The importance for MC5r and A2Ar expression in EAU to promote the induction of protective regulatory immunity, and the expression of MC5r and A2Ar on human immune cells, suggests that it may be possible to utilize the melanocortin-adenosinergic pathways to induce protective immunity in uveitic patients.

Vogt-Koyanagi-Harada syndrome: Perspectives for immunogenetics, multimodal imaging, and therapeutic options.

Vogt-Koyanagi-Harada syndrome (VKH) is a bilateral, diffuse granulomatous uveitis associated with neurological, audiovestibular, and dermatological systems. The primary pathogenesis is T-cell-mediated autoimmune response directed towards melanocyte or melanocyte-associated antigens causing inflammation of the choroidal layer. This phenomenon usually leads to diffuse inflammatory conditions throughout most parts of eye before ocular complications ensue. The diagnosis is achieved mainly by clinical features according to the revised diagnostic criteria of VKH published in 2001, without confirmatory serologic tests as a requirement. However, ancillary tests, especially multimodal imaging, can reliably provide supportive evidence for the diagnosis of early cases, atypical presentations, and evaluation of management. Prompt treatment with systemic corticosteroids and early non-steroidal immunosuppressive drug therapy can lessen visually threatening ocular complications and bring about good visual recovery. Close monitoring warrants visual stabilization from disease recurrence and ocular complications. This article review aims not only to update comprehensive knowledge regarding VKH but also to emphasize three major perspectives of VKH: immunogenetics as the major pathogenesis of the disease, multimodal imaging, and therapeutic options. The role of anti-vascular endothelial growth factor therapy and drug-induced VKH is also provided.

POOR PROGNOSTIC FACTORS IN PATIENTS WITH BIRDSHOT RETINOCHOROIDOPATHY.

PURPOSE: To identify prognostic factors for poor visual outcome in patients with birdshot retinochoroidopathy. METHODS: A case-control study of 98 patients with birdshot retinochoroidopathy (196 eyes) was evaluated with a follow-up period of at least 12 months. After exclusion of glaucoma, optic atrophy, and macular scar, the remaining eligible patients were categorized into two groups: poor visual outcomes and good visual outcomes. Poor visual outcome was defined as less than -6 mean deviation score on Swedish interactive threshold algorithm (SITA) short-wavelength automated perimetry (SWAP) test and abnormality (amplitude or implicit time) of 30 Hz flicker electroretinogram at 4-year follow-up and at the most recent visit for separate analysis. Potential factors between both groups were statistically analyzed by Chi-square test and logistic regression model. RESULTS: After the aforementioned exclusion, the remaining 77 patients with an average follow-up period of 52 ± 29 months (335 person-years, 36% with follow-up of more than 5 years) were divided into two groups. Sixteen patients were categorized as having poor visual outcome. Univariate analysis identified significant association of abnormal 30 Hz flicker electroretinogram amplitude (P = 0.004), implicit time (P = 0.002), and SITA SWAP mean deviation at the initial visit (P < 0.001) in the poor visual outcome group. Multivariate logistic regression analysis identified only SITA SWAP mean deviation to be associated with poor visual outcome (adjusted odds ratio, 32.50; 95% confidence interval [3.84-275.32]; P = 0.001) at the initial visit. To verify the model validity, an analysis of 42 patients at 4-year follow-up was performed and the outcome was confirmed (adjusted odds ratio, 8.80; 95% confidence interval [1.58-49.16]; P = 0.013). CONCLUSION: Worse SITA SWAP mean deviation at the initial visit is a predictor of poor visual outcome in patients with birdshot retinochoroidopathy, and may serve as a proxy marker for delayed effective steroid sparing therapy in patients with birdshot retinochoroidopathy.

Outcome of tocilizumab treatment in refractory ocular inflammatory diseases.

PURPOSE: To report the outcomes of tocilizumab treatment for refractory ocular inflammatory diseases. METHODS: A retrospective case series of 17 patients (28 eyes) diagnosed with recalcitrant ocular inflammatory diseases including uveitis (10 cases), scleritis (six cases) and orbital pseudotumour (one case), who received tocilizumab between April 2010 and March 2015. All patients were initiated with treatment of 4 mg/kg or 8 mg/kg tocilizumab. The primary outcome was absence of inflammation and achievement of steroid sparing at 6 and 9 months. Secondary outcomes were change in visual acuity and major adverse effects of tocilizumab causing discontinuation of the treatment. RESULTS: Mean age at initiation of tocilizumab was 41 ± 16 years. Prior to tocilizumab treatment, all patients underwent unsuccessful conventional immunosuppressive therapy while 94% of patients (16/17) failed treatment with various biological agents. After tocilizumab administration, control of inflammation and steroid sparing were achieved in 63% and 71% of uveitis patients at 6 and 9 months, while 50% of scleritis patients achieved the primary outcome at 6 and 9 months. Mean duration of tocilizumab therapy was 12.6 ± 10.0 (range, 2-35) months. Three of four patients who had a follow-up of at least 18 (range, 18-35) months experienced quiescent inflammation for up to 32 months of tocilizumab use until last visit. Four patients (24%) discontinued tocilizumab due to serious side effects including neutropenia, unacceptable dizziness and nausea, severe angioedema and severe abdominal pain. CONCLUSION: Our series demonstrated moderate efficacy of tocilizumab in recalcitrant uveitis and scleritis. Serious adverse effects were not uncommon.

ANALYSIS OF THREE-DIMENSIONAL CHOROIDAL VOLUME WITH ENHANCED DEPTH IMAGING FINDINGS IN PATIENTS WITH BIRDSHOT RETINOCHOROIDOPATHY.

PURPOSE: To describe changes in three-dimensional choroidal volume and thickness with full raster scans of enhanced depth imaging optical coherence tomography in patients with birdshot retinochoroidopathy. METHODS: This prospective case series collected spectral domain optical coherence tomography images with the enhanced depth imaging technique from eight eyes of eight patients with birdshot retinochoroidopathy including four active patients (four eyes) and four quiet patients (four eyes). Fifty scans of each patient were manually segmented before automated built-in calibration software was used. RESULTS: Of all active patients, there were no statistically significant differences in the total choroidal volume and mean central choroidal thickness between the active and inactive phase over 6 months of follow-up. Alterations in choroidal parameters were evident and consistent after amelioration of inflammation, whereas the retinal volume and thickness remained stable. Regarding the eight inactive eyes at 6 months, the mean total choroidal volume and mean central choroidal thickness were significantly less than historical controls (P = 0.03 and P < 0.001, respectively). Persistent suprachoroidal hyporeflective space in two patients was noted despite the fact that clinical inflammation completely subsided at 6 months. CONCLUSION: Choroidal volume and thickness changes were consistent with inflammation in patients with birdshot retinochoroidopathy. Patients with inactive birdshot retinochoroidopathy have significant reduction in choroidal volume and thickness than do normal patients.

Short-Wavelength Automated Perimetry Parameters at Baseline and Following Remission in Patients With Birdshot Retinochoroidopathy.

PURPOSE: To identify changes in short-wavelength automated perimetry patterns and parameters between the active and inactive states. DESIGN: Retrospective cohort study with age-matched, normal controls. METHODS: setting: Private tertiary referral center. STUDY POPULATION: Seventy-five eyes of 38 patients with active birdshot retinochoroidopathy and 37 eyes of 37 historical normal controls. INTERVENTION: Thirty-seven patients received immunomodulatory therapy. A fluocinolone acetonide intravitreal implant (Retisert) was implanted in both eyes of 1 patient as an initial treatment. MAIN OUTCOME MEASURES: Changes in short-wavelength automated perimetry total deviation scores, pattern deviation scores, mean deviation, and pattern standard deviation in the active phase and the remission state. RESULTS: Mean deviation (P = .006), pattern standard deviation (P = .001), total deviation score (P = .002), and pattern deviation score (P = .007) were significantly different from the active phase to the remission state. The length of time required to achieve remission did not significantly affect the changes in mean deviation (regression coefficient = 0.01; P = .92), pattern standard deviation (regression coefficient = 0.01; P = .87), total deviation score (regression coefficient = -0.1; P = .32), or pattern deviation score (regression coefficient = 0.1; P = .36) from the active phase to the remission state. CONCLUSION: There was significant improvement in total deviation score, pattern deviation score, mean deviation, and pattern standard deviation on short-wavelength automated perimetry as patients achieved remission. Short-wavelength automated perimetry appears to be a useful and complementary modality in monitoring disease activity in birdshot retinochoroidopathy.

Ocular involvement in systemic lupus erythematosus.

PURPOSE OF REVIEW: Many patients suffer from the ocular manifestations associated with systemic lupus erythematosus (SLE). Retinal vasculitis and optic neuritis are two of the most vision-threatening complications that can be associated with the disease. Ocular manifestations are often associated with wide-spread systemic inflammation which can be fatal. Thus, immediate recognition and treatment is vital for a positive outcome. RECENT FINDINGS: There is an array of medications available to ophthalmologists for treating the ocular manifestations of SLE. Treating the underlying systemic disease is crucial, as well as treating the active ocular complications. Recently, more attention has been placed on evaluating biologic agents' efficacy in treating the systemic condition. New therapies continue to emerge that have the potential to provide benefit to patients suffering from SLE. SUMMARY: SLE is a serious systemic condition that may first present with ocular manifestations. Thus, it is crucial for ophthalmologists to be equipped with the knowledge to detect and adequately treat the disorder to avoid vision/life-threatening complications. More research is needed to determine which therapy provides the best outcome for patients with limited side-effects.

Actin-dependent mitochondrial internalization in cardiomyocytes: evidence for rescue of mitochondrial function.

Previously, we have demonstrated that the transplantation of viable, structurally intact, respiration competent mitochondria into the ischemic myocardium during early reperfusion significantly enhanced cardioprotection by decreasing myocellular damage and enhancing functional recovery. Our in vitro and in vivo studies established that autologous mitochondria are internalized into cardiomyocytes following transplantation; however, the mechanism(s) modulating internalization of these organelles were unknown. Here, we show that internalization of mitochondria occurs through actin-dependent endocytosis and rescues cell function by increasing ATP content and oxygen consumption rates. We also show that internalized mitochondria replace depleted mitochondrial (mt)DNA. These results describe the mechanism for internalization of mitochondria within host cells and provide a basis for novel therapeutic interventions allowing for the rescue and replacement of damaged or impaired mitochondria.