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Purpose: To report a case of Cogan-Like Syndrome following treatment with nivolumab for metastatic cutaneous melanoma., Methods: A case report., Results: A 54-year-old female sought a second opinion from us regarding the recently diagnosed uveitis in both eyes. She had a diagnosis of metastatic cutaneous melanoma in the right arm and was undergoing treatment with nivolumab. Four weeks following the initiation of nivolumab therapy, she experienced tinnitus and bilateral sensorineural hearing loss, which was treated with oral and intratympanic steroids. While tapering the oral steroids, she developed iridocyclitis with papillitis in both eyes. This combination of vestibuloauditory symptoms and ocular inflammation was strikingly reminiscent of Cogan's syndrome. Because of the timing in relation to the nivolumab therapy and the steroid responsiveness of her presentation, this was speculated to be due to immune overactivation from the nivolumab. Given her complex condition, which involved toxicity and multiple metastases, the patient was advised to consider either topical and/or local corticosteroids or intravenous immunoglobulin. The patient chose to persist with corticosteroid therapy., Conclusion: Nivolumab could potentially be linked to an immune-related condition resembling Cogan syndrome. In cases involving patients with a complex condition necessitating nivolumab treatment, the use of topical and/or local corticosteroids or intravenous immunoglobulin, might constitute the sole viable treatment options.

Purpose: To evaluate outcomes of intravenous (IV) tocilizumab (TCZ) in patients with pars planitis refractory to conventional immunomodulatory therapy and anti-tumor necrosis factor (TNF) alpha agents., Methods: Medical records of eight patients diagnosed with pars planitis and treated with monthly 4 or 8 mg/kg IV TCZ were reviewed. The primary objective was to initiate and sustain remission continuously for three consecutive months. Secondary outcome measures were changes in best corrected visual acuity (BCVA), degree of anterior chamber (AC) inflammation, vitreous cell, vitreous haze, presence of vitreous or pars plana exudates, peripheral vasculitis, fluorescein angiography (FA) score and central subfieldthickness (CST) on macular optical coherence tomography (OCT)., Results: Fourteen eyes of eight patients were treated with IV TCZ. Seven patients were women. The average age was 31.35 ± 16.42 years. In 6 (75%) out of 8 patients, IV TCZ, either as monotherapy or in combination with another conventional immunomodulatory agent, induced and sustained remission. The average FA score reduced from 11.15 ± 3.52 at the baseline visit to 6.50 ± 2.12 at the one-year follow-up visit (p-value < 0.05). None of the patients experienced any side effects of IV TCZ., Conclusion: IV Tocilizumab (TCZ) may represent an effective and safe treatment option for patients diagnosed with pars planitis resistant to conventional immunomodulatory therapy and anti-TNF alpha agents.

Background: To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgically induced scleral necrosis (SISN)., Methods: Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main outcome measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months., Results: Forty-six (65.7%) patients were women, and the median age was 66 (range: 24-90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1-480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p  = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p  < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p  < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p  = 0.002) than non-autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group ( p  = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi ., Conclusions: Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.

Purpose: To characterize various ocular inflammatory complications arising from metastatic cutaneous melanoma therapies and their management., Methods: Retrospective case series of patients who were referred to a tertiary uveitis practice for ophthalmic exam All patients received targeted metastatic cutaneous melanoma treatment, including BRAF/MEK inhibitors and various immunotherapies., Results: 109 patients were identified, with 43 (39.4%) having 65 definitive instances of OIAE. Sixteen different OIAE were identified. Ipilimumab monotherapy and ipilimumab/nivolumab combination therapy were most commonly associated. Anterior uveitis was the most common OIAE (18/65, 27.7%). Thirty patients (69.8%) were managed with observation or topical steroid therapy. Only 4 patients required further therapies for OIAE, with one patient not attaining resolution., Conclusions and Relevance: While a broad range of OIAE was identified, most were not vision-threatening and did not require discontinuation of the associated therapy.

Purpose: To search findings that can explain the heterogeneity between Resistant and Responsive patients with birdshot chorioretinopathy., Patients and Methods: This was a retrospective observational case series on "Responsive" versus "Resistant" birdshot chorioretinopathy., Results: One-hundred-eighty and Ninety-nine patients were included in the Responsive and Resistant groups respectively. Multivariate analysis of paraclinical variables at the first visit demonstrated that mean deviation (p = .04), pattern standard deviation (p < .001), optic nerve head leakage (p = .012), large vessel leakage and staining (p = .01), and macular small vessel leakage (p = .03) were statistically significantly different between the two groups; however, at the visit preceding successful therapy, only macular small vessel leakage (p = .01) was statistically significantly different between the two groups., Conclusion: .Small vessel leakage in the macular area and/or optic nerve head leakage at the earliest visit might be risk factors for resistant birdshot chorioretinopathy.

Aim: To evaluate the effect of repository corticotropin injection (RCI) on regulatory T cell population in patients with noninfectious retinal vasculitis., Patients and Methods: Patients with active noninfectious retinal vasculitis were included in a prospective nonrandomized open-label study., Results: Eighteen patients (33 eyes) were included in the study. Eleven (61.1%) patients [20 (60.6%) eyes] and 7 (38.9%) patients [13 (33.3%) eyes] were in the responsive and non-responsive groups, respectively. We did not find any statistically significant difference within the PPP-R group, within the PPP-NR group, or between these two groups in regard to regulatory T cell population. No significant systemic or ocular complications were found., Conclusion: RCI may be a complementary treatment in patients with non-infectious retinal vasculitis with or without uveitis. This study did not demonstrate an increase in regulatory T cell population in patients with noninfectious retinal vasculitis.

Purpose: To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis., Patients and Methods: This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL., Results: Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage ( p = .005), the presence of vasculitis ( p = .01), the presence of active choroiditis ( p = .01), and the presence of CME on OCT ( p = .008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation ( p < .001) and the last follow-up visit ( p = .014) in the AVLL group., Conclusion: The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.

Purpose: To examine the diagnostic and prognostic roles of serum interleukin-6 levels in patients with uveitis., Methods: This was a retrospective observational case series. Demographic and clinical characteristics were compared between Group One (sixty patients) with normal serum IL-6 levels and Group Two (twenty patients) with high serum interleukin-6 levels., Results: Mean IL-6 level was 1.77 ± 0.97 pg/ml and 10.2 ± 9.7 pg/ml in Group One and Group Two respectively. Age, presence of systemic disease, and mean number of flare-ups were statistically significant ( p = .015, p = .000, p = .03, respectively). Multivariate analysis was performed on variables that were statistically significant in univariate analysis and showed that three variables had significant correlation with IL-6 levels in both groups: systemic disease (OR = 10.83, p < .001), Age (OR = 0.95, p = .03) and number of flare-ups (OR = 2.9, p = .02)., Conclusion: Serum IL-6 levels can provide diagnostic and prognostic information in regard to the course of disease and its treatment.

Purpose: To evaluate the parameters of the Fixed-Luminance and Multi-Luminance flicker electroretinography protocol among patients with early active birdshot chorioretinopathy., Methods: Fixed-Luminance magnitude, Fixed-Luminance phase, Multi-Luminance magnitude area under the curve, and Multi-Luminance phase area under the curve parameters were compared between early active birdshot chorioretinopathy patients and an age-matched control group., Results: There was no statistically significant difference between the Fixed-Luminance flicker magnitude ( P = .6), the Fixed-Luminance flicker phase ( P = .9), and the Multi-Luminance flicker phase area under the curve ( P = .55) when each was compared to the normal population; however, the difference between the mean Multi-Luminance flicker magnitude area under the curve in our patients and the healthy control group was statistically significant. ( P = .003)., Conclusions: Multi-Luminance flicker magnitude area under the curve has been shown to be significantly different from the normal population in the early active course of the disease., Abbreviations: BSCR: birdshot chorioretinopathy; cd: Cadmium; ERG: Electroretinography; FA: Fluorescein angiography; FL-: Fixed-luminance; HVF: Humphrey visual field; Hz: Hertz; ICG: Indocyanine green; m 2 : Square meter; ML-: Multi-luminance; ms: millisecond; SITA: Swedish interactive thresholding algorithm; SWAP: Short wave-length automated perimetry.

Purpose : To demonstrate the reliability of conjunctival biopsy analyzed by direct immunofluorescence (DIF) and supplemented with avidin-biotin complex immunoperoxidase (ABC) in diagnosing oMMP, and report therapy response in biopsy-positive patients, particularly when previously biopsy-negative elsewhere. Methods : Retrospective outcomes review of 136 consecutive patients after conjunctival biopsy for suspected oMMP. Results : Among 136 patients, 66% were diagnosed with oMMP by DIF and 13% via supplemental ABC immunoperoxidase. Sensitivity increased from 79.6% with DIF to 95.6% with supplemental ABC. Among 57 biopsy-positive patients, 77% were in remission at 1-year follow-up and 88% after 2 years. Of 34 previous biopsy-negative but now biopsy-positive patients with a 2-year follow-up, 91% achieved remission, including all 16 diagnosed via DIF and ABC. Conclusion : Conjunctival biopsy analyzed by histopathology and DIF supplemented by ABC has high reliability for diagnosing oMMP and is a useful tool to use before starting long-term immunomodulatory therapy in a patient with suspected oMMP.

Introduction: We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5 years in a subspecialty noninfectious uveitis population., Methods: Retrospective data from 5,530 noninfectious uveitis patients were abstracted by expert reviewers, and contemporaneous associations of VA with demographic and clinical factors were modeled., Results: Patients were a median of 41 years old, 65% female, and 73% white. Eyes diagnosed ≥5 years prior to cohort entry had worse VA (-1.2 lines) than those diagnosed <6 months prior, and eyes with cataract surgery performed prior to entry had worse VA (-5.9 lines) than those performed during follow-up. Vitreous haze (-4.2 lines for 3+ vs quiet), hypotony (-2.5 lines for ≤5 mm Hg vs 6-23 mm Hg), and CNV (-1.8 lines) all were strongly associated with reduced VA., Conclusion: Factors associated with reduced VA included well-known structural complications, and lack of subspecialty care during cataract surgery.

Introduction : We evaluated visual acuity (VA) over 5 years in a subspecialty noninfectious uveitis population. Methods : Retrospective data from 5,530 noninfectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up. Results : Patients were a median of 41 years old, 65% female, and 73% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each P < .001), then remained stable, except posterior uveitis mean VA worsened to initial levels. Conclusion : Mean VA of uveitic eyes improved and, typically, improvement was sustained under uveitis subspecialty care. Because VA tends to improve under tertiary care, mean VA change appears a better outcome for clinical studies than time-to-loss of VA.

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.

Aim: To determine the efficacy and safety of intravenous tocilizumab in refractory juvenile idiopathic arthritis associated uveitis., Patients and Methods: This was a retrospective observational case series. Patients with refractory juvenile idiopathic arthritis associated uveitis, who had received tocilizumab were included in this study., Results: 8 patients (14 eyes) were included in this study. The average age of the patients at the first visit was 16.8 ± 11.2 years (7-40). The average duration of follow-up period after starting treatment was 28.6 ± 24.6 months (9-70). Intravenous tocilizumab infusions induced and maintained remission in 5 patients (8 eyes). Vasculitis was resolved within 8 months in all but one patient. The presence of papillitis before starting treatment was directly correlated with visual acuity improvement. No side effects were observed., Conclusion: Intravenous tocilizumab infusion can be an effective and safe method of treatment to induce and maintain remission in resistant juvenile idiopathic arthritis associated uveitis.

Purpose: To report the visual prognosis, electroretinography (ERG) and perimetry outcomes of systemic corticosteroid-sparing immunomodulatory treatment (IMT) for birdshot retinochoroidopathy (BSRC)., Methods: Retrospective non-comparative case series of 132 patients (264 eyes) with BSRC treated with IMT from Massachusetts Eye Research and Surgery Institution., Results: The average follow-up time was 60.1 months. After one year on IMT, 39.4% showed no clinically active inflammation. After 5 years of IMT, 78.0% had no signs of clinical inflammation. No significant differences were observed on best-corrected visual acuity (BCVA), ERG parameters, and perimetry parameters between baseline and subsequent visits on IMT., Conclusion: Long-term systemic corticosteroid-sparing IMT was associated with a low rate of BSRC disease exacerbation. While differences were seen on testing parameters, they were not consistent trends and difference were attributed to variability of testing or fluctuation of inflammation that may be expected in the course of the disease.

Purpose: Frequent steroid drops represent a challenge in patient compliance. This study evaluated the safety and efficacy of 5 minute topical dexamethasone sodium phosphate-Visulex (DSP-Visulex) treatment regimen (two applications on the first week then weekly after) compared to daily prednisolone acetate 1% (PA) for noninfectious anterior uveitis., Materials and Methods: Forty-four patients were randomized to 8% DSP-Visulex with placebo eye drops (8% group, n = 14), 15% DSP-Visulex with placebo eye drops (15% group, n = 15), or Vehicle-Visulex with PA eye drops (PA group, n = 15). Patients received daily eye drops and Visulex treatments on days 1, 3, 8, and 15 with an optional treatment on day 22. Efficacy measures were change in anterior chamber cell (ACC) count from baseline and proportion of patients with zero ACC count at days 8, 15, and 29. Safety measures were adverse events (AEs), visual acuity, ocular symptoms, and intraocular pressure (IOP)., Results: ACC resolution over time was similar among the three groups. The percentage of patients with clear ACC was 18%, 22%, and 15% on day 8; 27%, 56%, and 54% on day 15; and 90%, 88%, and 77% on day 29 for the 8%, 15%, and PA groups, respectively. The numbers of reported AEs were 10, 36, and 12 for the 8%, 15%, and PA groups, respectively. Ten patients among all groups experienced treatment-related AEs, which included headache, eye pain, corneal abrasion, conjunctival/corneal staining, conjunctivitis, visual acuity reduction, and keratitis all of which were resolved during the timeframe of patients' participation in the study. IOP elevation was noted in the PA group throughout the study, whereas IOP elevation in the DSP-Visulex groups was observed at day 3 but not thereafter., Conclusions: The efficacy of the DSP-Visulex applications was comparable to the daily PA drops in the treatment of noninfectious anterior uveitis. Both 8% and 15% DSP-Visulex treatments were safe and well tolerated.

Purpose : To analyse pooled data from 2 similar phase 3 noninferiority studies comparing difluprednate 0.05% versus prednisolone acetate 1% in patients with endogenous anterior uveitis. Methods : Patients received difluprednate alternating with vehicle or prednisolone acetate for 14 days (8 drops/day in both groups), followed by tapering from day 14 to 28. All patients were observed until day 42. Results : More patients on difluprednate than on prednisolone acetate were cleared of anterior chamber cells on day twenty one (71.3% vs 54.7%; p  = 0.02); results were similar at the other time points. Treatment withdrawals were higher with prednisolone acetate than difluprednate (19.8% vs 7.4%; log-rank p  = 0.02). Study discontinuation due to lack of efficacy was also higher with prednisolone acetate than difluprednate (14.0% vs 0%; p  = 0.0002 [pre-specified exploratory analysis]). Conclusions : More difluprednate-treated eyes were quiet following 21 days of treatment, and difluprednate-treated patients were much less likely to be withdrawn from the study because of treatment failure.

Purpose : To describe the distribution, clinical findings, visual outcomes, treatment, and complications of children with uveitis at a tertiary referral ophthalmic center. Methods : Retrospective cohort study. We reviewed the medical records of all patients ≤16 years with uveitis referred to Massachusetts Eye Research and Surgery Institution from March 2005 to July 2016. Results : Of 286 included children, 62.24% were female. Mean age of onset was 8.4 years. The uveitis was mainly anterior (61.9%), recurrent (68.53%), bilateral (81.82%), and noninfectious (96.5%). Idiopathic cases accounted for 51.4%. The most frequent systemic association was juvenile idiopathic arthritis (34.96%). The majority of patients (78.32%) experienced complications. All patients, except one, needed systemic therapy. Conclusion : Pediatric uveitis is challenging to diagnose and manage, with frequent and potentially severe complications. Most cases were bilateral, recurrent, and idiopathic. Prompt referral to uveitis-specialized centers and an appropriate systemic therapy are mandatory for good visual outcomes.

Purpose : To review early withdrawal of immunomodulatory therapy (IMT) for birdshot retinochoroidopathy (BSRC). Design : Retrospective case-series of sixteen patients with Human-leukocyte-antigen-A29-positive BSRC treated with IMT ≥ 1 year and discontinued prior to achieving durable remission, observed ≥ 6 months off IMT. Results : Mean duration on IMT was 42.4 months. At discontinuation, quiescence was achieved in 75.0% of eyes. Subjects off IMT for 6 months, 1 year, and 3 years showed quiescence in 75.0%, 77.8%, and 80.0% of eyes. No significantly decreased vision was found 6 or 12 months after discontinuation. One eye experienced significantly decreased vision following 3 years without IMT. Significantly decreased amplitude on electroretinography and worse deviation parameters in perimetry were found in patients 3 years after withdrawal that experienced early discontinuation when compared with those achieving durable remission on IMT > 2 years (p < 0.05). Conclusion : The possibility of electroretinography and perimetry results worsening after early IMT discontinuation remained if the patients couldn't achieve remission.

Purpose : To assess the long-term efficacy and safety of IVIg monotherapy in patients with recalcitrant ocular cicatricial pemphigoid (OCP). Methods : A chart review of all OCP patients seen at the Massachusetts Eye Research and Surgery Institution (MERSI) between 2005 and 2015 was completed. Stage was graded by using the Foster grading system. IVIg infusion was 2g/kg/cycle administered in 3 consecutive days monthly. Results : Of 512 OCP patients, 17 patients (34 eyes) treated with IVIg monotherapy were identified. Seven were female and ten were male. The average age at diagnosis was 60.7-year-old. The follow up time ranged from 12 to 140 months. Twenty-six eyes (76.5%) achieved remission. Nine remission eyes received cataract surgeries, and 2 of them had relapse (22.2%). The other 17 eyes did not undergo ocular surgery and remained in remission. IVIg monotherapy showed high efficacy in stage 1 OCP (7/7, 100%). Ocular surgery can be associated with OCP relapse (Table 2). Conclusions : IVIg monotherapy is an effective and safe therapy in patients with recalcitrant OCP. Ocular surgery can be associated with OCP relapse.

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.

Purpose: To describe clinical manifestations, diagnostic approaches, therapy, and outcomes of biopsy-proven intraocular lymphoma., Methods: Review of tertiary referral center records between 2005 and 2015., Results: A total of 51 eyes of 26 patients were included; mean age of onset was 60.42 years. Common ocular complaints included floaters (42%) and blurred vision (35%); 62% of patients had ocular and central nervous system involvement; 11% had systemic lymphoma; and 27% had only ocular involvement. Vitreous analysis was positive for malignant cells in 77% of patients on initial biopsy, and in 100% of patients on repeat biopsy. In total, 20/26 patients received systemic and topical treatment before IOL diagnosis was made; 25 patients received intravitreal methotrexate and/or rituximab; one patient received intracameral rituximab. All patients achieved remission by their final visit., Conclusions: Intraocular lymphoma often masquerades as intraocular inflammation, resulting in delayed or misdiagnosis with subsequent inappropriate management. Optimal therapy is a challenge for oncologists and ophthalmologists.

Aims: To evaluate the efficacy and safety of rituximab (RTX) induction and maintenance treatment for patients with scleritis and granulomatosis with polyangiitis (GPA), Wegener's., Methods: Nine patients (12 eyes) with scleritis with GPA who did not respond to corticosteroids and more than one immunosuppressive agent who received ongoing maintenance RTX treatment were identified. Demographics and outcome measures were recorded., Results: Median follow-up time of 30 months (range, 15 to 87 months). All 12 eyes achieved remission during the RTX maintenance period with a median time in remission of 14 months (range, 5-76 months), and median interval between RTX initiation and inactive disease of 5 months (range, 2-8 months). Two eyes in two patients relapsed. One received steroid eye drops, and the other received a short-term increased dose of intravenous corticosteroids., Conclusions: RTX was effective as an induction and maintenance treatment in our small cohort of patients with GPA-associated scleritis.

Purpose: To evaluate the efficacy of chlorambucil in the treatment of serpiginous choroiditis., Methods: Patient records from the Massachusetts Eye Research and Surgery Institution (MERSI) were reviewed from over the past 10 years. In total, 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil were identified. QuantiFERON gold was negative in all of them. Chlorambucil was started at 0.15 mg/kg and dosage was titrated up using weekly white blood cell (WBC) count to achieve a target cell number of 3.0-4.5 × 10 9 cells/L. The goal of therapy was to maintain this value for at least 6-9 months. Adverse effects, recurrence, rate of new choroidal neovascularization (CNVM), and visual acuity before and after treatment were recorded., Results: The mean age of the 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil was 46 years, and six patients (35%) were male. The mean duration of treatment for chlorambucil was 8.4 months. None of them developed cancer or persistent side-effects, with a mean follow-up of 53 months. Of the patients, 12 (71%) achieved an average of 45 (5-120) months drug-free remission in their last follow-up. Visual acuity of 33 treated eyes remained within two lines of Snellen acuity in 27 eyes (82%), improved in one eye (3%), and deteriorated in five eyes (15%). Leukopenia was the most common side-effect, which was reversible in all cases., Conclusions: Chlorambucil in a relatively short duration of time, with an escalating dose guided by weekly WBC was well tolerated, as well as effective in preventing recurrence and maintaining vision in patients with serpiginous choroiditis.

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.

Purpose: To report use of intravenous foscarnet or cidofovir for the treatment of refractory acute retinal necrosis (ARN)., Methods: Retrospective chart review., Results: Four immunocompetent men aged 45-90 years presented with ARN from 2008-2014. One patient with two prior episodes of herpes simplex virus (HSV) ARN developed ARN after 6 years of antiviral prophylaxis. His condition worsened on acyclovir followed by intravenous foscarnet but responded to intravenous cidofovir (final VA in involved eye 20/20). Another patient with HSV ARN had received prolonged acyclovir prophylaxis for HSV keratitis; ARN improved after switching from acyclovir to intravenous foscarnet (final VA 20/125). Two patients with varicella zoster virus (VZV) ARN initially responded to acyclovir but developed fellow eye involvement 2-8 weeks later that worsened on acyclovir but responded to intravenous foscarnet (fellow eye final VA 20/20, 20/40)., Conclusions: Cases of HSV or VZV ARN that worsen despite intravenous acyclovir treatment may respond to intravenous foscarnet or cidofovir.

Purpose: To describe the clinical and molecular implications of a novel mutation in the NOD2/CARD15 gene on a family and its seven affected members., Methods: We reviewed the clinical presentations of family members who came to our center for refractory uveitis. Genetic testing and molecular testing was performed., Results: All affected members had adult onset recurrent non-granulomatous panuveitis. The inheritance pattern suggested an autosomal dominant disease and genetic analysis identified a novel mutation in the NOD2 gene that converted amino acid 600 from glutamate to alanine (E600A). Transfection of the E600A NOD2 into human embryonic kidney-293 (HEK293) cells revealed constitutive activation and a reduced ability to respond to the NOD2 ligand, muramyl dipeptide (MDP) as compared with wild-type NOD2., Conclusions: The E600A mutation in the NOD2 gene may confer a higher penetrance of uveitis but a later onset of milder forms of non-ocular involvement.

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.

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.

Purpose: Herpes simplex-associated uveitis is usually considered a unilateral eye disease, and rarely included in the differential diagnosis whenever there is bilateral involvement. We report three cases of bilateral herpetic anterior uveitis., Methods: We evaluated three patients who presented with clinical manifestations of bilateral uveitis suggestive of viral origin., Results: We found intraocular hypertension, cells in the anterior chamber, paralytic mydriasis, iris atrophy with transillumination defects, and variable anterior vitreous cellularity. According to the clinical findings, supported with herpes-specific antibody titers and aqueous humor PCR results in two of them, they were diagnosed with bilateral anterior herpetic uveitis., Conclusions: Our patients were initially misdiagnosed as having non-infectious uveitis and were treated with immunomodulatory medications, which could have favored the extension of infection bilaterally. Although uncommon, bilateral herpetic uveitis should always be considered in the differential diagnoses, when patients present with hypertensive uveitis in both eyes.

Purpose: To evaluate adalimumab as an immunomodulatory treatment for non-infectious ocular inflammatory diseases., Methods: Characteristics of patients treated with adalimumab were abstracted in a standardized chart review. Main outcomes measured were control of inflammation, corticosteroid-sparing effect, and visual acuity., Results: In total, 32 patients with ocular inflammation were treated with adalimumab. The most common ophthalmic diagnoses were anterior uveitis, occurring in 15 patients (47%), and scleritis, occurring in 9 patients (28%). At 6 months of therapy, among 15 eyes with active inflammation, 7 (47%) became completely inactive, and oral prednisone was reduced to ≤10 mg/day in 2 of 4 patients (50%). On average, visual acuity decreased by 0.13 lines during the first 6 months of treatment. Adalimumab was discontinued because of lack of effectiveness in four patients within 6 months., Conclusions: Adalimumab was moderately effective in controlling inflammation in a group of highly pre-treated cases of ocular inflammatory disease.

Purpose: To report our experience using intravenous infliximab for the treatment of tissue melt after Boston keratoprosthesis (B-KPro) types I and II in patients with autoimmune disease., Methods: Case series., Results: We identified four patients who were treated with intravenous infliximab in the context of tissue melt after B-KPro. Stevens-Johnson syndrome-associated corneal blindness was the primary surgical indication for B-KPro implantation in all patients. Two patients received a B-KPro type I and two patients received a B-KPro type II. The patients received intravenous infliximab for skin retraction around B-KPro type II, melting of the carrier graft or leak. Treatment resulted in a dramatic decrease in inflammation and, in some cases, arrest of the melting process. Cost and patient adherence were limiting factors to pursuing infliximab therapy. In addition, one patient developed infusion reactions., Conclusions: Intravenous infliximab may be considered as globe- and sight-saving therapy for tissue melt after B-KPro.

Purpose: To assess corticosteroid- and immunosuppressive therapy (IST)-free long-term remission in the treatment of patients with sympathetic ophthalmia (SO), a vision-robbing disease that can span a lifetime., Methods: The medical records of 19 patients with SO aged 16.1 to 94.95 years (median age 58.56 years) with median follow-up of 7.10 years (mean, 6.41; range, 2.5 to 8.63 years) were retrospectively examined., Results: All patients achieved control of inflammation, 13 of them for 2 years or more. Three (15.78%) of the 19 patients maintained remission without IST and corticosteroids for more than 5 years with vision of 20/25 or better in the sympathizing eye. Thirteen patients (68.42%) were inactive on IST or corticosteroids or in combination therapy. Eleven patients (57.9%) maintained visual acuity of 20/40 or better at the end of follow-up., Conclusion: Even with a devastating and possibly lifelong disease like sympathetic ophthalmia, long-term remission off all IST and corticosteroids, and perhaps even cure, is possible.

Uveitis is a common and serious complication of juvenile idiopathic arthritis. Up to 75% of all cases of anterior uveitis in childhood are associated with juvenile idiopathic arthritis. Despite the remarkable progress in early detection and treatment of inflammation, vision-threatening complications of uveitis still occur in almost 60% of patients. Structural complications include band keratopathy, maculopathy (macular edema, macular cysts, and epiretinal membrane), glaucomatous optic neuropathy, and cataracts. The management of complications in juvenile idiopathic arthritis is usually complex and requires early surgical intervention. In this paper, we review the general concepts of common ocular complications seen in patients with JIA-associated uveitis, with special attention to the recent diagnostic and preferred treatment approaches at the Massachusetts Eye Research and Surgery Institution. Received 9 March 2015; revised 30 September 2015; accepted 30 October 2015; published online 14 January 2016.

To describe how a multifocal fundus imaging system assisted the early diagnosis of cat scratch neuroretinitis in a case of a 27-year-old male with unilateral visual loss, neuroretinitis, and a peripapillary angiomatous lesion. Multimodal fundus imaging analysis was an essential contributor to the clinical diagnosis of cat scratch neuroretinitis during the early stage of the disease.

Purpose: To evaluate outcomes of long-term follow-up of Retisert multiple implantation and dissociation in eyes with chronic noninfectious uveitis., Methods: Review of 187 consecutive Retisert implants. Outcomes of multiple implantation and spontaneous medication pellet-strut dissociation were evaluated., Results: A total of 187 consecutive Retisert implants were reviewed. Eight implants were removed. The prevalence of spontaneous dissociation was 2.6% (5/187). The rate of dissociation increased to 11.11% (2/18) in cases of multiple implants. The mean period between Retisert implantation and spontaneous dissociation was 65.05 months. The mean period between implants in the same eye was 55.25 months. In cases of multiple implantations the old implant was not removed and 17.64% (3/17) of eyes required glaucoma filtering surgery., Conclusion: The rate of spontaneous dissociation of Retisert medication pellet-strut in eyes with single implant for noninfectious uveitis is low, which tends to increase in eyes with multiple implants.

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.

Purpose: The purpose of this review is to comprehensively explain the differential diagnosis of juvenile idiopathic arthritis-associated uveitis., Methods: Web-based literature review., Results: Main diagnostic decisions are made through a thorough anterior segment exam and a comprehensive exploration of past medical and family history., Conclusions: High clinical suspicion of other uveitic entities occurring in children is necessary and must be excluded by the practitioner before immediate diagnosis of juvenile idiopathic arthritis is made.

Chronic uveitides can lead to serious sequlae over time including blindness. Human Leukocyte antigen (HLA) plays an important role in immunological response of the eyes. Some of these uveitides are associated with certain Human Leukocyte antigen (HLA) types. This article reviews these relationships and their significance.

Purpose: To compare the efficacy and safety of cyclosporine/mycophenolate mofetil (CSA/MMF) and cyclosporine/azathioprine (CSA/AZT) in Vogt-Koyonagi-Harada (VKH) patients., Methods: Retrospective comparative case series with follow-up period of at least 1 year. Outcomes include remission rate and corticosteroid-sparing effect., Results: A total of 10 patients were included (5 patients in CSA/MMF, 5 patients in CSA/AZT). The remission rates for CSA/MMF and CSA/AZT were 5.3 and 5.6, respectively (p = .96). The median time to remission was 15 months for CSA/MMF group and 7 months for CSA/AZT group (p = .6419). The rates of corticosteroid-sparing effect were 7.9 and 5.0 for the CSA/MMF and CSA/AZT groups, respectively (p = .65). The median time to corticosteroid-sparing effect was faster in the CSA/AZT group (2 months) compared to the CSA/MMF group (13 months) (p = .9625). Approximately 50% of patients failed with the presented IMT combination regimens., Conclusions: No statistically significant difference was found in the two regimens from the study as presented, although the median time to remission and to corticosteroid-sparing effect was shorter for the CSA/AZT combination.

Purpose: Serpiginous choroidopathy (SC) is an inflammatory disease of unknown etiology. Infectious diseases that mimic SC are termed serpiginous-like choroidopathy (SLC). The aim of this study is to determine the clinical features of infectious SLC in comparison to SC., Methods: Multicenter case series. Variables analyzed were age, gender, laterality, visual acuity, intraocular inflammation, multifocal pattern, choroidal neovascularization, involvement of juxtapapillary area, and posterior pole. Statistical significance was assessed by Mann-Whitney U test and Fisher's exact test., Results: Twenty-four patients had SC and 5 patients had SLC. Mean ages were 50 and 46 years (SC and SLC, respectively). In the SC group, 54% of the patients were males, and in the SC group, 80% were males. The disease was bilateral in 87.5% in the SC group and in 80% in the SLC group. The juxtapapillary area was involved in 91% in SC eyes and 0% in the SLC group (p < .05)., Conclusions: In cases where the peripapillary area is disease-free, an infectious etiology has to be strongly suspected, as an immunomodulatory treatment could have severe consequences.

Purpose: To describe the evaluation of optical coherence tomography (OCT) scans in the Muliticenter Uveitis Steroid Treatment (MUST) trial and report baseline OCT features of enrolled participants., Methods: Time-domain OCTs acquired by certified photographers using a standardized scan protocol were evaluated at a reading center. Accuracy of retinal thickness data was confirmed with quality evaluation, and caliper measurement of centerpoint thickness (CPT) was performed when retinal thickness data were unreliable. Morphological evaluation included cysts, subretinal fluid, epiretinal membranes (ERMs), and vitreomacular traction., Results: Of the 453 OCTs evaluated, automated retinal thickness was accurate in 69.5% of scans, caliper measurement was performed in 26%, and 4% were ungradable. Intraclass correlation was.98 for reproducibility of caliper measurement. Macular edema (centerpoint thickness ≥ 240 μm) was present in 36%. Cysts were present in 36.6% of scans and ERMs in 27.8%, predominantly central. Intergrader agreement ranged from 78 to 82% for morphological features., Conclusion: Retinal thickness data can be retrieved in a majority of OCT scans in clinical trial submissions for uveitis studies. Small cysts and ERMs involving the center are common in intermediate and posterior/panuveitis requiring systemic corticosteroid therapy.

Although the phenomenon of fundus autofluorescence has been known for decades, it has only recently been recognized as a measure of retinal pigment epithelial function and health. Characteristic fundus autofluorescence patterns have been described in eyes affected by inflammation of the posterior segment, and these patterns have provided insights into the pathogenesis of posterior uveitis entities. In addition, preliminary data indicate that fundus autofluorescence characteristics may serve as markers of disease activity, allow prediction of visual prognosis, and may help determine the adequacy of therapy. We provide an overview of the current state of fundus autofluorescence imaging technology and review our current knowledge of fundus autoflourescence findings and their clinical use in the posterior uveitis entities.

Context: Retrospective case series, database study and literature review. Forty case reports are described., Objective: To report a possible association between fluoroquinolones and uveitis., Materials and Methods: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization, and Food and Drug Administration were collected on uveitis associated with systemic fluoroquinolone therapy. A literature review was performed using keywords "uveitis", "fluoroquinolones", and each individual fluoroquinolone name. Additional case reports were collected from the practices of six uveitis subspecialists and one neuro-ophthalmologist., Main Outcome Measures: Data garnered from the reports include the type of fluoroquinolone, age, gender, adverse drug reaction (ADR), dosage, duration of therapy until onset of uveitis, concomitant drugs, systemic disease, dechallenge and rechallenge data., Results: A total of 40 case reports of uveitis associated with fluoroquinolones were identified including 12 men, 27 women, and 1 case in which the gender was not specified. The median age was 54 years. Dosage varied between the different fluoroquinolone drugs, with the median dosage within the range recommended in the package insert for each different fluoroquinolone. Median time from beginning of therapy to appearance of the ADR was 13 days (range 0-20 days). Thirteen patients were 60 years or older, and one patient was taking systemic anti-inflammatory steroids. There were five positive dechallenge case reports., Discussion: According to World Health Organization criteria, the relationship between fluoroquinolone therapy and uveitis is "possible". Causality assessments are based on the time relationship of drug administration, uveitis development, and dechallenge data., Conclusions: Clinicians should be aware of a possible bilateral fluoroquinolone-associated uveitis, particularly the finding of iris transillumination and pigment dispersion.