Full Thickness Macular Hole in Aesthetician Occurring Due to Accidental Self-exposure to Cosmetic Laser Machine Trying to Take Special Precautions Against COVID-19.

A 25-year-old aesthetician was operating Q-switch pulse (SPECTRA) cosmetic laser machine of 1,064 nm wavelength, for the purpose of skin bleaching. The probe suddenly slipped over the plastic sheet that had been placed to avoid COVID-19 exposure after which she complained of sudden loss of vision. She was diagnosed as having vitreous hemorrhage in her right eye and was treated conservatively for one month. She then complained of central scotoma and was diagnosed to have developed a full-thickness macular hole, for which she was advised vitrectomy surgery. The purpose of this case report is to emphasize the importance of taking precautions during the COVID-19 era and while doing that making sure how to handle the machines so as not to inflict any accidental injury to the operating physician. Macular Holes following skin bleaching with Nd:YAG laser occurring in operating aesthetician is rare as compared to that occurring in the patients.

COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM AT PEDIATRIC AGE: Surgical Versus Conservative Approach.

PURPOSE: To report outcomes of pediatric patients with combined hamartoma of the retina and the retina pigment epithelium followed up conservatively or after pars plana vitrectomy. METHODS: This retrospective multicenter study included 62 eyes of 59 pediatric patients with combined hamartoma of the retina and the retina pigment epithelium from 13 different international centers with an average age of 7.7 ± 4.7 (0.3-17) years at the time of the diagnosis and having undergone pars plana vitrectomy or followed conservatively. At baseline and each visit, visual acuity values, optical coherence tomography for features and central foveal thickness, and tumor location were noted. Lesions were called as Zone 1, if it involves the macular and peripapillary areas, and the others were called as Zone 2 lesions. RESULTS: Twenty-one eyes of 20 patients in the intervention group and 41 eyes of 39 patients in the conservative group were followed for a mean of 36.2 ± 40.4 (6-182) months. Best-corrected visual acuity improved in 11 (68.8%) of 16 eyes in the intervention group and 4 (12.9%) of 31 eyes in the conservative group ( P < 0.001). The mean central foveal thickness decreased from 602.0 ± 164.9 µ m to 451.2 ± 184.3 µ m in the intervention group, while it increased from 709.5 ± 344.2 µ m to 791.0 ± 452.1 µ m in Zone 1 eyes of the conservative group. Posterior location of tumor, irregular configuration of the foveal contour and ellipsoid Zone defect in optical coherence tomography, subretinal exudate and prominent vascular tortuosity were associated with poor visual acuity. CONCLUSION: Vitreoretinal surgery is safe and effective in improving vision and reducing retinal distortion in Zone 1 combined hamartoma of the retina and the retina pigment epithelium in children.

Comparison of RetCam and Smartphone-Based Photography for Retinopathy of Prematurity Screening.

This study aimed to compare the clinical performance between a smartphone-based fundus photography device and a contact imaging device for retinopathy of prematurity (ROP) screening. All patients were first examined with binocular indirect ophthalmoscopy (BIO), which served as the reference standard. The patients were then assessed by two devices. Imaging quality, ability to judge the zone and stage of ROP, agreement with the BIO results, vital signs, and pain scores were compared between these two devices. In total, 142 eyes of 71 infants were included. For the smartphone-based fundus photography, image quality was graded excellent or acceptable in 91.4% of examinations, although it was still significantly inferior to that of the contact imaging device (p < 0.001). The smartphone-based fundus photography images had moderate agreement with the BIO results regarding the presence or absence of plus disease (Cohen's κ = 0.619), but evaluating the zone (p < 0.001) and stage (p < 0.001) of ROP was difficult. Systemic parameters, except for heart rate, were similar between the two imaging devices (all p > 0.05). In conclusion, although the smartphone-based fundus photography showed moderate agreement for determining the presence or absence of plus disease, it failed to identify the zone and stage of ROP.

Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study.

The present study aimed to determine the efficacy and safety of pro re nata (PRN) intravitreal brolucizumab therapy for neovascular age-related macular degeneration (AMD) without a loading dose in the real-world setting. The PROBE study (Pro Re Nata Brolucizumab for Exudative AMD) is a retrospective, observational, multicentric study that included 27 treatment-naïve patients (27 eyes) with neovascular AMD who received PRN brolucizumab therapy with the treatment interval being at least 8 weeks, should the need for a second consecutive injection arise. The primary outcome measure was changed to best-corrected visual acuity (BCVA) over time. Secondary outcome measures included the determination of change in central subfield thickness (CST) and complications. The mean follow-up was 11.2 ± 1.2 months. The mean baseline and final BCVA were 57.4 ± 4.5 letters and 65.3 ± 3.12 letters, respectively (p = 0.014). The mean gain in letters at the end of follow-up was 7.8 ± 3.5 letters. There was a significant decrease in CST at the end of the follow-up period (p = 0.013). Patients received a mean of 2.2 ± 0.9 injections (in addition to the first mandatory injection) during the follow-up period. There were no adverse events noted. In conclusion, initial PRN brolucizumab for exudative AMD without a loading dose demonstrated significant visual improvement and no adverse events.

Endogenous Endophthalmitis A Complication of COVID-19 Pandemic: A Case Series.

PURPOSE: To report six patients with endogenous endophthalmitis as a complication of COVID-19 infection. METHODS: A multicentric retrospective database review of patients with a diagnosis of endogenous endophthalmitis and a history of COVID-19 infection. RESULTS: Four of six patients were diabetics. All presented after an average duration of 40 days (Range 17-90 days) of COVID-19 infection. Two of six patients had bilateral involvement. Five of six patients had received intravenous corticosteroid for COVID-19. Two of six vitreous samples showed fungi (Candida and Bipolaris species), two showed bacteria (Staphylococcus species) and two samples were culture negative. Control of infection with good visual outcome in four out of eight eyes. CONCLUSIONS: COVID-19 patients with a history of hospitalization and prolonged use of systemic corticosteroids and comorbidities, for example, diabetes mellitus have a high risk of endogenous endophthalmitis. A high index of clinical suspicion with timely intervention can salvage many eyes.

Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - An update.

Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.

Efficacy and Safety of Intravitreal Sirolimus for Noninfectious Uveitis of the Posterior Segment: Results from the Sirolimus Study Assessing Double-Masked Uveitis Treatment (SAKURA) Program.

PURPOSE: To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS). DESIGN: Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies. PARTICIPANTS: Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] ≥1.5+ on modified Standardization of Uveitis Nomenclature scale). METHODS: Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 µg (n = 208), 440 µg (n = 208), or 880 µg (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-µg group was terminated after interim results found no significant difference in efficacy compared with the 440-µg dose. MAIN OUTCOME MEASURES: The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events. RESULTS: A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 µg compared with 44 µg intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-µg and 44-µg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-µg and 44-µg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-µg and 44-µg groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups. CONCLUSIONS: Intravitreal sirolimus 440 µg improved ocular inflammation, as measured by VH, compared with the 44-µg dose, with minimal impact on IOP, while preserving BCVA.

The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings.

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.

Intravitreal ziv-aflibercept in diabetic vitreous hemorrhage.

BACKGROUND: To evaluate the safety and efficacy of intravitreal ziv-aflibercept (IVZ) in the management of vitreous hemorrhage (VH) in eyes with previously lasered proliferative diabetic retinopathy (PDR). METHODS: In a prospective multicenter study, previously lasered eyes who had dense VH from PDR underwent intravitreal injection of ziv-aflibercept (IVZ) (1.25 mg aflibercept). Demographic characteristics of the patients, baseline and final logMar visual acuity, number of injections, VH clearance time, and need for vitrectomy were recorded. RESULTS: Twenty-seven eyes of 21 patients were included in the study. Mean age of study patients was 61.3 ± 14.1 years with mean duration of diabetes mellitus of 22.6 ± 7.8 years. Mean logMAR BCVA at baseline was 1.41 ± 1.26 (Snellen equivalent 20/514) and at the last visit 0.55 ± 0.61 (Snellen equivalent 20/70) with a mean gain of 0.86 EDTRS line (paired student t test = 5.1; p ≤ 0.001). Mean number of IVZ 2.4 ± 1.6 (range 1-6). The mean follow-up time was 11.7 ± 11.1 months (range 1-34). Mean time for visual recovery and/or VH clearance was 5.7 ± 3.3 weeks. Eyes, which required multiple injections, the interval period between injections for recurrent VH was 6.4 ± 5.2 months. No subject required vitrectomy. No ocular or systemic adverse effects were noted. CONCLUSIONS: IVZ injections had good short-term safety and efficacy for the therapy of new or recurrent VH in previously lasered eyes with PDR reducing somewhat the need for vitrectomy.Trial registration: NCT02486484.

Standardization of Nomenclature for Ocular Tuberculosis - Results of Collaborative Ocular Tuberculosis Study (COTS) Workshop.

Purpose: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).Methods: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.Results: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes.Conclusion: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity.

Evaluation of Choroidal Layer Thickness in Central Serous Chorioretinopathy.

PURPOSE: To evaluate medium and large choroidal vessel layer thickness (MCVT and LCVT, respectively) in eyes with acute and chronic central serous chorioretinopathy (CSC) in comparison with age-matched controls. METHODS: The study included 96 eyes of 96 patients with CSC, including 53 eyes with acute CSC, 43 eyes with chronic CSC, and 30 eyes of 30 age-matched normal subjects. Manual measurements of subfoveal choroidal thickness (SFCT), MCVT, and LCVT at subfoveal and 750 µm nasal and temporal to the fovea locations were made on enhanced depth imaging optical coherence tomography (EDI-OCT) of the macula in all subjects using ImageJ software (National Institutes of Health, Bethesda, MD, USA). RESULTS: SFCT in acute CSC was significantly larger than that in healthy eyes (P = 0.0001). SFCT in acute CSC did not differ significantly from that in chronic CSC eyes. Subfoveal LCVT and MCVT in acute CSC eyes were greater than those in healthy eyes (P = 0.02 and P = 0.03, respectively). Mean SFCT and MCVT in chronic CSC eyes were significantly larger than those in control eyes (P = 0.01 and P = 0.04, respectively). No significant difference in LCVT was observed between chronic and control eyes. CONCLUSION: Choroidal vasculature is altered in both acute and chronic CSC. SFCT, MCVT, and LCVT are higher in eyes with acute CSC. The thickening of medium choroidal vessels is still detectable in chronic CSC compared to control eyes.

Long-term visual outcome and its predictors in macular oedema secondary to retinal vein occlusion treated with dexamethasone implant.

BACKGROUND: To evaluate the functional long-term outcome in patients with macular oedema (MO) secondary to central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) treated with dexamethasone implant (DEX implant) and to identify its clinical predictors. METHODS: A 24-month, retrospective, multinational, real-world study. Chart review of patients with either naïve or recurrent MO secondary to CRVO/BRVO treated with DEX implant, including best-corrected visual acuity (BCVA), central subfield thickness (CST), demographic baseline characteristics and details of any additional treatment during follow-up. RESULTS: A total of 155 eyes (65 CRVO, 90 BRVO) from 155 patients were included. At 24 months, mean BCVA did not change significantly in CRVO (-2.1±24.5 letters, p=0.96) and BRVO patients (1.3±27.0 letters, p=0.07). A worse baseline BCVA (p<0.001), visual acuity (VA) gain ≥5 letters at 2 months (p=0.006) and no need for adjunctive intravitreal therapy after first DEX implant (p=0.001) were associated with a better final BCVA gain. Treatment-naïve patients (p=0.006, OR: 0.25, 95% CI 0.11 to 0.57) and those with a baseline CST≤400 µm (p=0.02, OR: 0.25, 95% CI 0.10 to 0.63) were identified as being less likely to need additional intravitreal therapy. CONCLUSION: Clinical baseline characteristics and the early treatment response were identified as possible predictors for long-term outcome and the need of adjunctive intravitreal therapy in MO secondary to BRVO/CRVO treated by DEX implant.

Safety of 5914 intravitreal ziv-aflibercept injections.

PURPOSE: To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions. METHODS: This was a retrospective, observational study which included patients from 14 participating centres who received IVZ. The medical records of patients who received IVZ from March 2015 through October 2017 were evaluated. Patient demographics and ocular details were compiled. Ocular and systemic adverse events that occurred within 1 month of IVZ injections were recorded and defined as either procedure-related or drug-related. RESULTS: A total of 1704 eyes of 1562 patients received 5914 IVZ injections (mean±SD: 3.73±3.94) during a period of 2.5 years. The age of patients was 60.6±12.8 years (mean±SD) and included diverse chorioretinal pathologies. Both ocular (one case of endophthalmitis, three cases of intraocular inflammation, and one case each of conjunctival thinning/necrosis and scleral nodule) and systemic adverse events (two cases of myocardial infarction, one case of stroke and two deaths) were infrequent. CONCLUSION: This constitutes the largest pooled safety report on IVZ use and includes patients from 14 centres distributed across the globe. It shows that IVZ has an acceptable ocular and systemic safety profile with incidences of adverse events similar to those of other vascular endothelial growth factor inhibitory drugs. The analysis supports the continued use of IVZ in various retinal disorders.

Intravitreal Sirolimus for the Treatment of Noninfectious Uveitis: Evolution through Preclinical and Clinical Studies.

In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1-3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 µg intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n = 50 and n = 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n = 24 and n = 347, respectively) suggested that 440 µg has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-µg group than in the 44-µg group (22.8% vs. 10.3%; P = 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1-3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 µg intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

Gender variation in central serous chorioretinopathy.

BACKGROUND: Comparison of presentation and outcomes of central serous chorioretinopathy (CSC) between male and female subjects in different ethnic populations. METHODS: Retrospective comparison between male and female subjects with CSC was completed. Demographic details, clinical presentations, imaging features and treatment outcomes were compared at baseline and at last follow-up. RESULTS: This study included 155 male and 155 female subjects with a mean (CSD) age of 43.8 ± 10.3 and 57.0 ± 12.1 years, respectively, and a mean duration of follow-up of 8.49 ± 12.6 months. At presentation, there was no difference in visual acuity; however, visual acuity was significantly higher for female subjects at last follow-up (p = 0.02). Optical coherence tomography (OCT) analysis showed that subretinal deposits (p < 0.001), hyperreflective foci (p = 0.001), retinal pigment epithelial detachment (p = 0.01) and retinal pigment epithelium (RPE) irregularities (p = 0.03) were higher in male subjects at presentation. Angiographic analysis showed that diffuse leakage and RPE tracts were common in males (p = 0.01 and p = 0.02). No significant differences in choroidal dilatation or diffuse choroidal leakages were noted. CONCLUSIONS: Female subjects with CSC appear to have better outcomes, with less chances of diffuse RPE damage and other OCT features compared to males.

Polypoidal choroidal vasculopathy: Pearls in diagnosis and management.

Polypoidal choroidal vasculopathy (PCV) is increasingly recognized as an important cause of exudative maculopathy in Asians as against Wet age-related macular degeneration in Caucasians. A panel of retinal experts methodically evaluated pertinent updated literature on PCV with thorough PubMed/MEDLINE search. Based on this, the panel agreed upon and proposed the current consensus recommendations in the diagnosis (clinical and imaging), management and follow-up schedule of PCV. Diagnosis of PCV should be based on the gold standard indocyanine green angiography which demonstrates early nodular hyperfluorescence signifying the polyp with additional features such as abnormal vascular network (AVN). Optical coherence tomography is an excellent adjuvant for diagnosing PCV, monitoring disease activity, and decision-making regarding the treatment. Current treatment modalities for PCV include photodynamic therapy, anti-vascular endothelial growth factor agents, and thermal laser. Choice of specific treatment modality and prognosis depends on multiple factors such as the location and size of PCV lesion, presence or absence of polyp with residual AVN, amount of submacular hemorrhage, presence or absence of leakage on fundus fluorescein angiography, visual acuity, and so on. Current recommendations would be invaluable for the treating physician in diagnosing PCV and in formulating the best possible individualized treatment strategy for optimal outcomes in PCV management.

SURGICAL OUTCOMES AND COMPLICATIONS OF RHEGMATOGENOUS RETINAL DETACHMENT IN EYES WITH CHORIORETINAL COLOBOMA: The Results of the KKESH International Collaborative Retina Study Group.

PURPOSE: To study the outcomes of management of rhegmatogenous retinal detachment in eyes with chorioretinal colobomas. METHODS: A retrospective review of 119 patients (119 eyes) with chorioretinal colobomas who underwent surgical repair for rhegmatogenous retinal detachment was performed. Data were collected on the site of the retinal break, type of surgery, anatomical success, and complications. RESULTS: The most common location of the primary retinal break was the intercalary membrane in 58.8% of eyes. The most common surgical intervention was vitrectomy with endolaser and silicone oil tamponade (77.3% of eyes). Final anatomical success was achieved in 87.4% of eyes. Anatomical success was significantly higher in eyes that received long-acting tamponade (P = 0.006). Cryotherapy was significantly associated with failure of primary vitrectomy (P = 0.028). Placement of an encircling band did not affect anatomical outcomes (P = 0.75). Most of the eyes (60%) with recurrent retinal detachment after primary vitrectomy had a primary break within the normal retina. CONCLUSION: The optimal option for managing retinal detachment in eyes with chorioretinal colobomas is pars plana vitrectomy with long-acting tamponade (silicone oil or octafluoropropane) and retinopexy to the edge of the coloboma and the primary breaks. Cryotherapy is associated with poor anatomical outcomes. An encircling band does not seem to affect the final anatomical outcome.

Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA).

PURPOSE: To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). DESIGN: Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. PARTICIPANTS: Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. METHODS: Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 µg, administered on Days 1, 60, and 120. MAIN OUTCOME MEASURES: The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. RESULTS: A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 µg (22.8%; P = 0.025) and 880 µg (16.4%; P = 0.182) groups met the primary end point than in the 44 µg group (10.3%). Likewise, higher proportions of subjects in the 440 µg (52.6%; P = 0.008) and 880 µg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 µg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 µg [63.6%], 440 µg [76.9%], and 880 µg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. CONCLUSIONS: Intravitreal sirolimus 440 µg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.