BACKGROUND AND OBJECTIVE:The CALM Registry was a retrospective cohort study that assessed real-world outcomes of treating chronic noninfectious uveitis affecting the posterior segment (NIU-PS) with the 0.18-mg fluocinolone acetonide implant (FAi). PATIENTS AND METHODS:Eligible participants were aged ≥18 years and diagnosed with chronic NIU-PS. Safety and effectiveness outcomes, as available, were collected from charts. RESULTS:Two hundred sixty-seven eyes from 200 participants received the FAi (mean age, 62.8 years; 10.5% phakic). Median intraocular pressure remained stable at 14.0 mmHg. Two cataract surgeries were reported. In the 12 months pre-FAi, 84.1% of eyes had ≥1 recurrence of uveitis; 12 months post-implant, the recurrence rate was 12.0%, and retinal thickness reduced significantly (P < .05). The proportion of eyes with ≥ 20/40 visual acuity was stable from baseline (49%) to 12 months (55%). CONCLUSION:Real-world data from the CALM Registry study indicate effective control of chronic NIU-PS with the FAi and no new safety signals.

Purpose To report the clinical and multimodal imaging (MMI) findings and long-term follow-up of stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) contiguous with midperipheral retinoschisis (MPRS) and to describe a severe SNIFR variant termed CARPET (Central Anomalous Retinoschisis with mid-PEripheral Traction). Design Retrospective case series. Subjects Eleven patients (15 eyes) with SNIFR contiguous with MPRS in at least one eye at baseline or final follow-up. Methods MMI features, including cross-sectional and en face macular and peripheral spectral-domain optical coherence tomography (OCT) and OCT angiography, were reviewed in all cases at baseline and at the final follow-up visit. Main Outcome Measures Various courses (including progression, regression, or stability) of MPRS or SNIFR over time were evaluated. Results MPRS exhibited centripetal progression to SNIFR in 5 eyes of 3 patients with follow up of 67, 60, and 27 months, respectively, with maintenance of excellent visual acuity (range: 20/25-20/20) in 4 of these 5 eyes. In 2 eyes of 2 patients (including 1 eye with initial centripetal progression of MPRS to SNIFR), MPRS contiguous with SNIFR spontaneously resolved with long-term follow-up (77 and 48 months, respectively). SNIFR contiguous with MPRS partially regressed after 48 months in one patient, and was stable after 54 months in another. A distinctive midperipheral microvasculopathy, associated with MPRS that was contiguous with SNIFR, was identified in 7 eyes of 4 patients. Finally, 3 eyes of 3 patients exhibited additional unique features, including central neurosensory detachment and outer lamellar macular hole, which were associated with significant midperipheral traction, representing a severe variant subtype of SNIFR that we refer to as CARPET. Two of these 3 eyes progressed with short-term follow-up of 6 and 2 months, respectively, while the schisis resolved and vision improved after pars plana vitrectomy in the third case. Conclusions MPRS can progress to SNIFR over multiple years of follow-up. SNIFR with MPRS can also spontaneously resolve or remain stable. MPRS can additionally be complicated by a midperipheral inner retinal microvasculopathy. Finally, CARPET may represent a unique and severe variant form of SNIFR driven by midperipheral vitreoretinal traction and associated with significant vision loss.

Background/aims To explore and characterise the clinical phenotype of acute anterior uveitis flares with delayed severity in patients with human leucocyte antigen B27 (HLA-B27)-associated anterior uveitis.Methods Retrospective chart review of patients with HLA-B27-associated anterior uveitis. Demographic and clinical data were recorded, as well as the clinical characteristics of acute anterior uveitis flares. A flare was considered to have delayed severity if any of the following criteria were met within 3-21 days of symptomatic onset: a two-step increase in anterior chamber inflammation on consecutive exams; a new development of hypopyon or fibrinoid aqueous reaction on consecutive examinations or a significant worsening of symptoms.Results A total of 371 patient charts were identified, of which 137 were included. 321 acute anterior uveitis flares were documented, with 36 (11.2%) meeting the criteria for a delayed severity flare. The average time from symptomatic onset was 10.2 days, and patients presented with an average anterior chamber cell grade of 3.5 in delayed severity flares compared with 1.6 in non-delayed severity flares. No significant difference in frequency of delayed severity presentation was noted based on the presence or absence of systemically associated rheumatological disease, papillitis on initial presentation and retinal vasculitis on initial presentation. The frequency of topical steroid therapy after symptomatic onset was not significantly different between the two flare phenotypes.Conclusions Our study presents the novel characterisation of a delayed severity phenotype of HLA-B27-associated acute anterior uveitis flares.

PURPOSE:To characterize the course of uveitis in ulcerative colitis (UC) patients following colectomy and assess whether uveitis activity arises and/or persists independently of colonic disease. METHODS:This is a retrospective case series from a tertiary uveitis referral center. Patients with non-infectious uveitis, a confirmed diagnosis of UC, and a history of colectomy were included. Clinical data were extracted, including demographics, ocular history, treatment regimens, and disease activity. Uveitis flares were defined as the presence of at least 1+ cells or flare in the anterior chamber, 1+ vitreous cells and/or haze or angiographic evidence of active inflammation as noted by the investigators. RESULTS:We identified 73 patients with UC-associated uveitis and 11 had a history of colectomy. Post-colectomy uveitis flares occurred in all 11 patients. Notably, eight patients experienced de novo uveitis activity following their colectomy. The remaining three uveitis patients had documented uveitis flares prior to colectomy. A total of 25 flares were documented, including multiple recurrences in three patients. One patient experienced 13 flares and ultimately required enucleation. Excluding this difficult case, patients with long-term follow-up (≥1 year) generally responded to topical steroid therapy. However, several flares occurred despite concurrent immunomodulatory therapy. CONCLUSION:This case series highlights that uveitis flares may persist or recur following colectomy in UC patients, supporting the hypothesis that uveitis activity can occur independently of intestinal inflammation. These findings support the need for continued ophthalmologic surveillance in UC patients post-colectomy.

Suprachoroidal triamcinolone acetonide (SCS-TA) injections were recently approved to treat macular edema secondary to noninfectious uveitis. However, its use in managing posterior scleritis has not been reported. We report the first case of SCS-TA used in the treatment of posterior scleritis. A 67-year-old woman with posterior scleritis complicated by exudative retinal detachment, diagnosed by spectral-domain optical coherence tomography scan (OCT), presented with pain, decreased vision, and redness in the left eye for 8 months. She was previously prescribed topical prednisolone and oral prednisone with minimal improvement. She also had a history of rheumatoid arthritis treated with multiple systemic immunosuppressive agents. After SCS-TA, the patient's pain resolved and visual acuity improved. OCT demonstrated significant reduction in sclerochoroidal thickening. Via its novel delivery method, SCS-TA may be an effective treatment for posterior scleritis. Further studies are needed to establish long-term efficacy and safety of this treatment modality.

To obtain physicians’ “real-world” perspectives on early experiences with triamcinolone acetonide suprachoroidal injection (SCS-TA) for treatment of patients with uveitic macular edema (UME). Twelve retina/uveitis specialists in the United States were surveyed about SCS-TA injection procedure and patient outcomes. Survey participants administered ≥ 291 SCS-TA injections to 243 patients with UME with various disease characteristics (etiologies, chronicity, and anatomical subtypes). Commonly reported reasons for SCS-TA adoption included potential for lowering the risk of steroid-associated intraocular pressure elevations versus intravitreal injections or implants (100

This study outlines a scenario involving unilateral periocular inflammation exhibited resistance to conventional immunomodulatory therapy (IMT) and biologic response modifying agents, which was successfully managed with oral cyclophosphamide monotherapy. A 39-year-old male visited our clinic, expressing discomfort and swelling in his left upper eyelid for six months. All multidisciplinary consultations and imaging yielded normal results. He remained consistently on a dosage of 50 mg oral prednisone. Blood tests yielded results within the normal range or were negative, with the exception of the antinuclear antibody. He did not respond to conventional IMT and biological response modifier agents. Ultimately, the patient began oral cyclophosphamide. One month after commencing cyclophosphamide treatment, the oral prednisone dosage was gradually reduced without any flare-up. oral cyclophosphamide can serve as a valuable treatment for periocular inflammation that does not respond to standard conventional IMT and biologic response modifier agents.

PURPOSE:The purpose of the study was to study the efficacy of oral cyclophosphamide monotherapy in advanced resistant ocular cicatricial pemphigoid (OCP). MATERIALS AND METHODS:This retrospective case series examines patients diagnosed with advanced resistant OCP at a uveitis tertiary care center who were treated with oral cyclophosphamide therapy. RESULTS:Seventeen patients were included in this study. The average age of the participants was 74.3 ± 10.3 years, ranging from 60 to 99 years. The gender distribution was 8 females to 9 males. Oral cyclophosphamide-induced remission in 7 patients (41.1%) and was prematurely discontinued in 10 patients (58.9%), with 7 (63.7%) citing ineffectiveness and 3 (36.3%) experiencing side effects as reasons for discontinuation. The average therapy dose of cyclophosphamide administered was 116.1 ± 47.5 mg. The average duration required for the induction of remission was 150 ± 128 days. The overall therapy duration averaged 306 ± 189 days. Conducting univariate logistic regression with generalized estimating equations (GEEs) on variables did not reveal statistically significant differences between the two groups (responsive and nonresponsive to oral cyclophosphamide therapy), except for the maximum dose of oral cyclophosphamide therapy (P = 0.007). CONCLUSION:The prognosis of advanced OCP in patients is unlikely to be altered by the stepladder approach and step-up strategy. While oral cyclophosphamide can be efficacious for remission induction in resistant and aggressive OCP cases, a step-down strategy employing less potent agents with safer side effect profiles should be contemplated for subsequent treatment.

BACKGROUND AND OBJECTIVE:A consensus exercise was carried out to address unmet needs in the classification, diagnosis, and management of patients with chronic noninfectious uveitis affecting the posterior segment (NIU-PS), with a focus on chronic postoperative inflammation/cystoid macular edema. METHODS:Eight experts participated in roundtable discussions and consensus-building exercises to develop clear guidelines for the diagnosis and management of chronic NIU-PS. The group addressed questions surrounding clinical features, diagnostic tests, and treatment considerations. RESULTS:Clinicians agreed that chronic uveitis/intraocular inflammation should be defined as having persistence or recurrence for 3 or more months. Diagnosis is informed by evaluation of signs and symptoms, use of imaging, and exclusion of infectious etiologies. Management should be initiated with the least invasive therapies, proceeding to intraocular injections, and/or long-term intravitreal or systemic therapies, as necessary. CONCLUSION:This article offers an up-to-date consensus guideline based on clinical experience. Future clinical trials may help to test and reevaluate these recommendations. [Ophthalmic Surg Lasers Imaging Retina 2024;55:652-658.].

Purpose To report a case of acute macular neuroretinopathy (AMN) after intravitreal triamcinolone acetonide (TRIESENCE®) injection for cystoid macular edema secondary to birdshot chorioretinopathy. Method A case report. Patient A 62-year-old female. Results The patient presented with acutely decreased vision and a ring scotoma around her central vision three days after intravitreal triamcinolone acetonide (TRIESENCE®) injection for cystoid macular edema in her right eye (OD) secondary to birdshot chorioretinopathy. She had undergone pars plana vitrectomy, cataract extraction, and secondary intraocular lens implantation OD three months prior to the recent injection. Best-corrected visual acuity (BCVA) was 20/1000 OD and 20/50 OS. Intraocular pressure was 21 mmHg OD and 12 mmHg OS. Fluorescein angiography demonstrated a hypofluorescent area in the perifoveal zone OD. Optical coherence tomography OD depicted hyperreflective areas in the outer nuclear layer, outer plexiform layer, and retinal pigment epithelium. We diagnosed her with AMN OD and started her on brimonidine three times a day OD. She came back a week later with resolved scotoma and her vision improved to 20/60 OD. Five weeks later, BCVA was 20/40 and Intraocular pressures (IOP) was 12 mmHg OD. Conclusions and importance Intravitreal triamcinolone injection may be a cause of AMN with cystoid macular edema (CME) and borderline-high intraocular pressure. Brimonidine may be an effective treatment for these patients in the early course of the disease.

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 compare vision acuity outcomes of long-term steroid therapy compared with immunomodulatory therapy for treatment of sympathetic ophthalmia. DESIGN:Single-center, retrospective, comparative clinical study. METHODS:Patients with sympathetic ophthalmia treated from March 2005 to October 2022 with at least 1 year of follow-up were included. Visual acuity outcomes were compared by steroid and immunomodulatory treatment modality. RESULTS:Thirty-five patients with sympathetic ophthalmia were included in the study, with follow-up ranging from 1 to 17 years. Higher rates of vision loss correlated with longer periods of active uveitis and steroid treatment. Lower rates of vision loss correlated with longer periods of uveitis remission on immunomodulatory therapy alone and drug-free remission. Treatment with alkylating agents or combination therapy with an antimetabolite, a biologic-response modifier, and cyclosporine are more likely to result in sympathetic ophthalmia remission. CONCLUSION:Immunomodulatory therapy leads to superior vision outcomes in cases of steroid-resistant or recurrent sympathetic ophthalmia. Steroid therapy may be useful for acute or recalcitrant sympathetic uveitis but is insufficient for long-term inflammatory control. PRéCIS: This manuscript describes a retrospective analysis of vision outcomes in patients with sympathetic ophthalmia. Results indicate that long-term immunomodulatory therapy is associated with better vision outcomes than long-term steroid therapy for sympathetic ophthalmia treatment.

Purpose: The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP). Methods: A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens–Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded. Results: A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2%) being positive. One hundred thirty-nine patients (21.5%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3%) had only 1 such condition, 35 (6.9%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9% of patients with sufficient follow-up. Conclusions: Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface.

Objective: To compare the demographic, clinical, ancillary testing, and multimodal imaging characteristics of birdshot chorioretinopathy (BSCR) patients with late recurrence and birdshot patients with durable remission. Patients and Methods: This was a retrospective observational case series. The above-mentioned parameters were studied in BSCR patients with late recurrence (group 1) and BSCR patients with durable remission (group 2). Results: Fifty-five patients were included in this study. The average age of patients was 62.1 +/- 11.1 years (range, 35-88 years). Groups 1 and 2 included 20 (36.4%) and 35 (63.6%) patients, respectively. In group 1, the average age of patients was 60.5 +/- 10.39 years (range, 35-79 years). The female-to-male ratio was 16:4. In group 2, the average age of patients was 63.1 +/- 11.6 years (range, 37-88 years). The female-to-male ratio was 22:13. None of the demographic, clinical, ancillary testing, and multimodal imaging parameters were statistically significantly different between the two groups. Using a receiver operating characteristics (ROC) curve, we found that the ideal duration of successful therapy to induce durable remission was 30 months with 70% sensitivity and 40% specificity (ideal point on the curve). A Kaplan-Meier survival curve demonstrated that late recurrence was seen within 30 months after stopping successful treatment of patients with BSCR. Conclusion: There are no demographic, clinical, ancillary testing, or multimodal imaging characteristics that can predict late recurrence in BSCR patients. However, we found that 30 months of successful treatment may be ideal and recommended.

BACKGROUND:Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE:We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS:Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS:Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS:Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.

Purpose: To study whether rituximab and bortezomib combination therapy is more effective than rituximab monotherapy in the treatment of non-paraneoplastic autoimmune retinopathy (npAIR). Methods: Retrospective case series involving six patients with npAIR, taking either rituximab and bortezomib combination therapy (three cases) or rituximab monotherapy (one case and two historical patients).Results: Patients on both treatment regimens showed stability in most of the visual function parameters during the one year of follow-up. Combination therapy resulted in improvement of scotopic combined rod and cone a-wave and b-wave amplitudes in all eyes where they were available (four eyes); however, rituximab monotherapy resulted in only two eyes with stable scotopic combined rod and cone a-wave and b-wave amplitudes, while four eyes showed a decrease in both a-and b-wave amplitudes. The average improvement in b-wave amplitude (50.7% +/- 29.4% [range, 25-90%]) was higher than the average improvement in a -wave amplitude (35.7% +/- 9.74 [range, 25-63%]). No severe adverse effects were reported.Conclusion: Rituximab and bortezomib combination therapy may not be more effective than rituximab monotherapy in npAIR patients for most of the visual function parameters; however, this combination therapy may be more effective in improving scotopic combined rod and cone a-and b-wave amplitudes. This may indicate the higher efficacy of combination therapy when there is involvement of the inner retina.

Objective: To investigate the clinical features, treatment, and visual outcome of occlusive retinal vasculitis (ORV), with a focal analysis on prognostic factors associated with poor visual outcome. Methods: We conducted a retrospective cohort study in patients diagnosed with ORV with at least 6 months of follow-up. Demographic data, ocular features, best corrected visual acuity (BCVA), fluorescein angiography, therapy regimens, and outcomes were collected from the Massachusetts Eye Research and Surgery Institution database from 2006 to 2017. Multivariate logistic regression was performed to analyze the factors independently predicting poor visual outcome. Results: Fifty-two patients (69 eyes) were enrolled, 42 with noninfectious cause, 9 with infectious cause, and 1 with maslupus erythematosus, and Beh??cet???s disease comprised the causes of ORV. Forty of the 42 patients with noninfectious ORV received immunomodulatory therapy (IMT), and 35 patients (87.5%) were able to achieve steroid-free remission. Compared with the BCVA at the initial visit (0.66 [??0.11] logMAR), there was significant improvement at the most recent visit (0.37 [??0.07] logMAR, p = 0.001). A multivariate analysis demonstrated that optic nerve atrophy, macular ischemia, and poor BCVA at initial presentation were independently correlated with poor visual outcome. Conclusions: ORV could be caused by a wide spectrum of systemic inflammatory diseases. Aggressive IMT is preferred to achieve a steroid-free durable remission for noninfectious ORV. Optic nerve atrophy, macular ischemia, and poor BCVA at the initial visit predict a poor visual outcome.

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.

We report 2 patients with chronic panuveitis who were treated with fluocinolone acetonide intravitreal implant (Yutiq, EyePoint Pharmaceuticals Inc, Watertown, MA) intended to control ocular inflammation long term without interfering with systemic immunity. The first case was a man in his 50s referred for ocular complaints in the setting of ongoing immunotherapy for the treatment of metastatic melanoma. He was diagnosed with bilateral drug-induced panuveitis. Treatment objectives were outlined as reduction of inflammation, prevention of uveitis recurrence, and continuation of systemic immunomodulatory therapy in order to maintain malignancy remission; the patient was treated with fluocinolone acetonide intravitreal implant bilaterally and at 18 months' follow-up had 20/20 bilateral visual acuity and no inflammation. In case 2, a woman in her 70s, presented with a 2-month history of worsening floaters and blurry vision. She was phakic, with bilateral nuclear sclerotic cataracts, 1+ vitreous cells and 2+ haze, diffuse vasculitis, and central leakage around the optic nerve and posterior pole. She was diagnosed with bilateral idiopathic panuveitis with retinal vasculitis. The patient continued to do well at 1 year following intravitreal implantation with fluocinolone acetonide.