Longitudinal analysis of aqueous humour cytokine expression and OCT-based imaging biomarkers in retinal vein occlusions treated with anti-vascular endothelial growth factor therapy in the IMAGINE study.

BACKGROUND/OBJECTIVES: Retinal vein occlusion (RVO) is the second most common retinal vascular disorder. Despite promising advances with anti-VEGF therapy, select patients are unresponsive to therapy. A precision medicine-based approach for therapeutic decision-making based on underlying biomarkers may facilitate treatment based on the underlying pathway. This study aims to identify the baseline and longitudinal cytokine profiles of RVO-related macular oedema and correlating these expression profiles with higher order OCT features using a novel retinal segmentation and feature extraction platform. SUBJECTS/METHODS: The IMAGINE study is a post-hoc assessment of aqueous humour cytokines with correlation to higher level analysis of imaging studies. OCT scans underwent machine learning enhanced segmentation of the internal limiting membrane (ILM), ellipsoid zone (EZ) and retinal pigment epithelium (RPE), as well as evaluating volumetric fluid metrics. Samples of aqueous humour were obtained at baseline, as well as months 4 and 9 prior to treatment. These samples were analysed for the expression of multiple cytokines. Patients were divided into Responders and Non-Responders based on OCT profiles. Additionally, patients were categorised as a Rebounder if their CST increased by 50% after initial improvement. RESULTS: Twenty-six eyes were included. The OCT-based response schema identified 21 Responders (81%) and 5 Non-Responders (19%). VEGF levels directly correlated with intraretinal fluid volume and angiogenin was inversely correlated with fluid indices. Multiple cytokines, including ANGPTL4, were directly correlated with ellipsoid zone disruption. The baseline VEGF levels were significantly higher in all responders compared to Non-Responders (p = 0.02). Rebounders tended to have significantly decreased levels of angiogenin and TIMP-1 (p = 0.019, p = 0.015). CONCLUSIONS: Cytokine expression was linked to specific OCT features and treatment response in RVO. Identification of an imaging phenotype that could serve as a surrogate for underlying active disease pathways could enhance treatment decision-making and precision medicine.

Severe retinal complications in Knobloch Syndrome - Three siblings without clinically apparent occipital defects and a review of the literature.

BACKGROUND: Knobloch syndrome results from recessive mutations in COL18A1 and is characterized by retinopathy and occipital scalp, brain and skull defects. METHODS AND MATERIALS: We report three siblings, born to consanguineous parents, two of whom with genetically confirmed Knobloch syndrome due to a homozygous pathogenic variant c.4054_4055del; p.Leu1352Valfs*72 in COL18A1. RESULTS: With the lack of classic occipital findings, an initial diagnosis of familial exudative vitreoretinopathy was entertained in these siblings because of the history of retinal detachments, retinal pigmentary changes and abnormal vitreous. The diagnosis of Knobloch syndrome was eventually made through molecular genetic testing using an extensive panel. In one patient presenting with acute retinal detachment and posteriorly dislocated intraocular lens implant, reattachment surgery was successful in stabilizing vision. CONCLUSION: The clinical diagnosis of Knobloch syndrome can be difficult to reach in the absence of the typical occipital scalp defects. A careful medical history, detailed clinical examination and molecular genetic testing will reveal the correct diagnosis of Knobloch syndrome in atypical cases.

Occlusive retinal vasculitis: novel insights into causes, pathogenesis and treatment.

PURPOSE OF REVIEW: Occlusive retinal vasculitis (ORV) has a large differential diagnosis and varied therapeutic approaches. This review highlights existing and novel causes and treatment options for ORV. RECENT FINDINGS: Mutations in CAPN5, TREX1, and TNFAIP3 have been associated with dominantly inherited forms of ORV. Various intraocular therapeutics have been shown to occasionally cause ORV; the most recent medications associated with ORV are vancomycin and brolucizumab. In cases of ORV linked to Behçet's disease, clinical trials support the use of tumor necrosis factor alpha inhibitors. SUMMARY: Identification of the underlying etiology of ORV is critical to help guide treatment. Treatment in ORV involves both treatment any underlying infection or autoimmune condition, cessation of the any offending causative agent and local treatment of neovascular complications.

Exploring the angiographic-biologic phenotype in the IMAGINE study: quantitative UWFA and cytokine expression.

BACKGROUND: This study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF) therapy in diabetic macular oedema (DME). METHODS: The IMAGINE DME study is a post hoc imaging biomarker and intraocular cytokine assessment from the DAVE study, a prospective DME clinical trial that included aqueous humour sampling and UWFA imaging. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated through multiplex arrays. UWFA parameters were assessed using an automated feature analysis platform to determine ischaemic and leakage indices and microaneurysm (MA) count. Eyes were classified into UWFA responder or non-responder groups based on longitudinal quantitative UWFA parameter improvement. Cytokine expression was correlated with UWFA metrics and evaluated in the context of therapeutic response. RESULTS: Twenty-one eyes were included with a mean age of 55±10 years. Increased panretinal leakage index correlated with VEGF (r=0.70, p=0.0005), angiopoietin-like 4 (r=0.77, p=4.6E-5) and interleukin (IL)-6 (r=0.64, p=0.002). Panretinal ischaemic index was associated with tissue inhibitor of metalloproteinases 1 (TIMP-1, r=0.49, p=0.03) and peripheral ischaemia correlated with VEGF (r=0.45, p=0.05). MA count correlated with increased monocyte chemotactic protein-4 (MCP-4, r=0.60, p=0.004) and platelet and endothelial cell adhesion molecule 1 (PECAM-1, r=0.58, p=0.005). Longitudinal MA reduction was associated with decreased baseline VEGF and urokinase receptor (uPAR) (p<0.05). High baseline VEGF and IL-6 were associated with dramatic reduction in macular leakage (p<0.05). CONCLUSIONS: Baseline and longitudinal quantitative UWFA imaging parameters correlated with multiple aqueous humour cytokine concentrations, including VEGF and IL-6. Further research is needed to assess the possible implications of using these findings for evaluating treatment response.

Panuveitis Presumed Secondary to Ibrutinib Therapy.

Although a small number of cases of secondary uveitis have been documented in the setting of ibrutinib therapy, panuveitis has not previously been described with this medication. The authors describe a presumed case of panuveitis in a patient on ibrutinib for chronic lymphocytic leukemia. The purpose of this report is to document a case of asymmetric, bilateral panuveitis in the setting of ibrutinib use. Panuveitis may develop in the setting of ibrutinib use, and local steroid therapy can be successfully used for treatment without cessation of systemic cancer therapy. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:160-164.].

Patient-Reported Complications after Intravitreal Injection and Their Predictive Factors.

PURPOSE: The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center. DESIGN: Retrospective, institutional review board-approved study. PARTICIPANTS: Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016. METHODS: Intravitreal injection. MAIN OUTCOME MEASURES: Complication occurrence within 15 days of injection. RESULTS: From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient's gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications. CONCLUSIONS: Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient's gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.

Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study.

PURPOSE: To identify biomarkers for predicting response to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype. DESIGN: The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial. METHODS: Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers. RESULTS: Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (-24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = -0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01). CONCLUSIONS: OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.

Optimizing Visualization of Membranes in Macular Surgery With Heads-Up Display.

BACKGROUND AND OBJECTIVE: To determine which optical parameter profiles (OPPs) can be utilized to improve the visualization of epiretinal membranes (ERMs) and the internal limiting membrane (ILM) using a three-dimensional heads-up microscope during 25-gauge pars plana vitrectomy. PATIENTS AND METHODS: Fourteen independent graders were asked to complete a questionnaire comparing each of the OPPs against the unaltered control image for each given surgical case. RESULTS: Analysis of the graders' responses indicated that higher values of hue are correlated with better visualization of ERM/ILM before and after dye application. There was overall agreement that OPPs could be used to enhance the visualization of the ERM and ILM during surgery. CONCLUSIONS: The use of OPPs to improve the visualization of specific structures is still new and heavily dependent on surgeon preference. The authors' study shows that some OPPs may enhance the visualization of the ERM and ILM during macular surgery. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:584-587.].

Inferior Corneal Haze and Inflammatory Endotheliopathy Related to Pars Planitis.

PURPOSE: To describe the finding of inferior corneal haze secondary to presumed inflammatory endothelio-10 pathy in a series of patients with pars planitis. METHODS: Single-center retrospective observational consecutive case-series. RESULTS: Seven patients with an established diagnosis of pars planitis are described in this case series including four females and three males. The ages ranged from 5 to 31 years at presentation. Pars planitis was bilateral in six patients and unilateral in one patient. Fundus examinations revealed vitreous opacities and pars plana exudates in all seven patients, cystoid macular edema in four patients, and peripheral retinal vasculitis in two patients. Corneal examination revealed opacification of the posterior cornea in an inferior location in 10 of the 13 eyes with pars planitis. Only one of these eyes had keratic precipitates. For a given patient, corneal involvement was more commonly seen in the more inflamed eye. In one patient with active inflammation, microcystic corneal edema was noted to predate the formation of inferior corneal endothelial opacification, suggesting that physical proximity to the site of inflammation at the inferior pars plana is the cause of this notable physical finding. CONCLUSIONS: Inferior posterior corneal haze related to inflammatory endotheliopathy may occur in eyes with pars planitis. As patients with pars planitis may be otherwise asymptomatic, this corneal finding shouldprompt a detailed funduscopic examination to rule out this form of uveitis.

Local therapy for cancer therapy-associated uveitis: a case series and review of the literature.

BACKGROUND/AIMS: Immunotherapy and targeted therapy for metastatic cancer may cause immune-related adverse events (irAEs) such as uveitis. If irAEs are severe or require systemic steroids, cancer therapy is often held or discontinued. Local steroid therapy for cancer therapy-associated uveitis allows the continuation of cancer therapy. This series demonstrates successful management of cancer therapy-associated uveitis with local therapy based on uveitis subtype. METHODS: This is an Institutional Review Board-approved retrospective case series of patients with uveitis secondary to immunotherapy or targeted therapy managed with local treatment, and focused literature review. RESULTS: Five patients (median age: 54, range 31 to 75) were included. Time to uveitis onset following cancer therapy initiation was 3 to 12 months. All patients received checkpoint inhibitor therapy; one patient additionally received targeted therapy. Two patients presented with anterior uveitis, two with panuveitis and one with posterior uveitis. Four of five patients demonstrated evidence of posterior segment inflammation on multimodal imaging. Anterior uveitis was successfully treated with topical prednisolone acetate 1% (PA 1%) alone, and posterior segment involvement recalcitrant to topical PA 1% was treated successfully with topical difluprednate, intravitreal triamcinolone acetonide or a combination. Patients with isolated anterior uveitis did not require maintenance topical therapy; those with posterior and panuveitis required chronic low-dose topical therapy. CONCLUSION: Based on our series as well as the existing literature demonstrating the use of local therapy for irAEs, we propose an approach to local therapy for cancer therapy-associated uveitis starting with topical steroids and initiating injectable steroids in cases of recalcitrant panuveitis or posterior uveitis. Subclinical inflammation on posterior segment imaging responds robustly to difluprednate or intravitreal steroid therapy, and patients with posterior segment involvement may require more aggressive management and long-term maintenance.

The use of biologics for uveitis associated with spondyloarthritis.

PURPOSE OF REVIEW: The term spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints, including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease, juvenile SpA and undifferentiated SpA. These diseases can also present with uveitis, or intraocular inflammation, which can be controlled with biologics. RECENT FINDINGS: Profound success has occurred with the tumor necrosis factor-α inhibitors infliximab and adalimumab, moderate success with certolizumab pegol and golimumab and less encouraging results with etanercept. Promising results have also been demonstrated with interleukin-17 (IL-17) antagonists, such as secukinumab ixekizumab or combined IL-12 and 23 medications, such as ustekinumab. SUMMARY: In cases of uveitis that require long-term control, biologics are an emerging and valuable class of medications for these patients, and may provide avenues to control both their underlying SpA and uveitis manifestations.

Sporadic Burkitt Lymphoma with Orbital Extramedullary Infiltration.

BACKGROUND/AIMS: Sporadic Burkitt lymphoma is rarely associated with orbital involvement. METHODS: We present a case of sporadic Burkitt lymphoma with extramedullary subperiosteal leukemic infiltrates of the orbit and facial bones. RESULTS: Follow-up examination after chemotherapy and disease remission reveals resolution of the subperiosteal infiltrates. CONCLUSION: Despite an aggressive presentation, cure is common with appropriate, intensive treatment. To our knowledge, this report is the first to photographically depict the resolution of extramedullary orbital subperiosteal leukemic infiltrates after appropriate chemotherapy.

Optic Nerve Compression From MIRAgel Implant Migration in a Monocular Patient.

The MIRAgel implantation was popularized in the 1980s as an alternative to silicone for scleral buckle retinal detachment repair. However, long-term follow-up has revealed that the implants can expand, creating globe compression and potentially visually devastating intraocular invasion. The authors document a 33-year-old monocular male patient presenting 20 years after MIRAgel implantation with extensive expansion, posterior migration, globe compression, and possible optic nerve compression. Debulking of the MIRAgel stabilized the vision and restored affected extraocular movements. The authors highlight that posterior MIRAgel migration can cause optic nerve compression, and implant debulking may require a multi-disciplinary approach. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:815-818.].

Treatment Duration and Side Effect Profile of Long-Term Use of Intravitreal Preservative-Free Triamcinolone Acetonide in Uveitis.

PURPOSE: Noninfectious uveitis has been treated historically with corticosteroid therapy in varying doses and routes. Triesence, a preservative-free sterile formulation of triamcinolone acetonide, has been used in a wide spectrum of ocular pathologies, but there have been few large studies validating its dosing or detailing long-term side effects in uveitic disease. The primary aim of this study was to describe the relative duration of action and side effects of 2 doses of preservative-free intravitreal triamcinolone acetonide (PF-IVTA) in uveitis. DESIGN: Retrospective, comparative consecutive case series. METHODS: Charts of all patients receiving PF-IVTA (2 mg or 4 mg) in a defined time period (2012-2014) at the Cole Eye Institute were examined for patient demographics, time to treatment failure (TTF), use of systemic immunosuppression, use of intraocular pressure-lowering therapies, date of cataract surgery and glaucoma filtration surgery, and adverse events. RESULTS: The final data set examined 514 injections in 214 eyes. Mean duration of follow-up was 1.5 years. There was similar demographic distribution between eyes that received 2 mg PF-IVTA only and eyes that received a combination of 4 + 2 mg PF-IVTA. No statistically significant difference in TTF between injection dosages was observed. There was a higher incidence of glaucoma filtering surgery and cataract surgery in eyes that received 4 + 2 mg PF-IVTA as well as a shorter time to glaucoma surgery, when compared to eyes that received 2 mg PF-IVTA alone. CONCLUSIONS: This retrospective study supports that 2 mg PF-IVTA displayed noninferior treatment duration to 4 mg PF-IVTA, and may carry a significantly lower side-effect profile of cataract development and glaucoma filtering surgery.

Mild Bilateral Hemorrhagic Occlusive Retinal Vasculitis Following Intracameral Vancomycin Administration in Cataract Surgery.

A patient underwent cataract surgery with prophylactic intracameral vancomycin (Vancocin; Pfizer, New York City, NY) in each eye, 2 weeks apart. Four weeks after, the patient presented with a mild bilateral hemorrhagic occlusive retinal vasculitis (HORV). A systemic work-up was negative for syphilis, toxoplasmosis, Bartonella, tuberculosis, and sarcoidosis. The patient was treated with oral steroids and one intravitreal steroid injection in the left eye. Ten months after presentation, the patient's vasculitis was quiescent. Although the literature describes primarily severe forms of HORV, the authors' case describes bilateral, mild HORV and highlights the potential underreporting of these cases in the literature. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:369-373.].

Paracanthal "One-Snip" Decompression in a Cadaver Model of Retrobulbar Hemorrhage.

PURPOSE: The authors assess the effectiveness of a modified paracanthal or "one-snip" procedure compared with the traditional lateral canthotomy and inferior cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a human cadaveric model of retrobulbar hemorrhage. METHODS: This study comprised a comparative interventional study in a cadaveric model of retrobulbar hemorrhage. Six orbits of 3 fresh cadavers were included in the study. Baseline measurements of IOP and proptosis were recorded for all 6 orbits before and after simulation of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3) underwent modified paracanthal or "one-snip" procedure. The primary outcome measures were reduction in IOP and proptosis between the 2 techniques. RESULTS: Following lateral canthotomy and inferior cantholysis of each right orbit, the average IOP dropped to 14 mm Hg (range of 11-18 mm Hg), corresponding to a mean decrease of 32 mm Hg. Following the "one-snip" procedure of each left orbit, the average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to a mean decrease of 22 mm Hg. There was no statistically significant difference in IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2 treatment groups. CONCLUSIONS: Compared with traditional lateral canthotomy xand inferior cantholysis, the modified paracanthal or "one-snip" procedure is effective for IOP reduction and led to mild improvement of proptosis in a cadaveric model of retrobulbar hemorrhage. The authors hope this study helps improve orbital compartment syndrome outcomes by providing an option that more providers will feel comfortable performing and therefore decreasing time to surgical decompression.

The Prevalence of Adverse Ocular Hemorrhagic Events in Patients Utilizing Oral Anticoagulant and Antiplatelet Therapy in Routine Clinical Practice.

BACKGROUND AND OBJECTIVE: Previous literature assessing ocular hemorrhagic complications of anticoagulant/antiplatelet medications in routine clinical practice is limited. This study evaluates the prevalence of spontaneous ocular hemorrhagic events associated with anticoagulation/antiplatelet therapy. PATIENTS AND METHODS: A retrospective study was performed to identify patients taking anticoagulants (rivaroxaban [Xarelto; Janssen Pharmaceuticals, Beerse, Belgium], bivalirudin [Angiomax; The Medicines Company, Parsippany, NJ], lepirudin [Refludan; Bayer HealthCare Pharmaceuticals, Berlin, Germany], dabigatran [Pradaxa; Boehringer Ingelheim, Ingelheim am Rhein, Germany], and argatroban) and antiplatelet agents (clopidogrel [Plavix; Bristol-Myers Squibb, New York City, NY], prasugrel [Effient; Lilly Medical, Indianapolis, IN], and ticagrelor [Brilinta; AstraZeneca, Cambridge, UK]) who presented for an eye examination. Location of hemorrhage, relevant systemic and ocular comorbidities, baseline demographics, and concomitant aspirin use were noted. RESULTS: A total of 44 patients with spontaneous ocular hemorrhage were identified. Thirty patients had a single episode, whereas 14 patients had multiple episodes (two or more hemorrhagic events). Prevalence of spontaneous ocular hemorrhage on prasugrel (7.2%) and rivaroxaban (3.1%) was higher compared to dabigatran (1.9%), clopidogrel (2.0%), and ticagrelor (2.7%). CONCLUSION: Prevalence of spontaneous ocular hemorrhage with use of anticoagulant/antiplatelet agents is higher in routine clinical practice as compared to previously reported literature. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:27-34.].

The application of optical coherence tomography angiography in uveitis and inflammatory eye diseases.

Since its introduction in the early 1990s, optical coherence tomography (OCT) has evolved in resolution and technological advances, and in recent years its initial application of assessing the morphology of a tissue has been implemented by the study of its functional blood flow, through optical coherence tomography angiography (OCTA). This novel technique details capillary networks by comparing the amount of light returned from static and moving targets without the need for intravenous dye administration. While this imaging modality has been used for various ocular conditions, the application OCTA to uveitis conditions remains sparse. This review aims to establish the basis of OCTA and its current application to ocular inflammatory disorders, with an emphasis on monitoring progression and response to treatment, as well as predicting visual complications. In particular, this review explores the use of OCTA in iris vessel dilation seen in various forms of iritis, as a predictive factor for further episodes of inflammation. OCTA can also depict ischemia in the deep plexus layers of the retina and identify true choroicapillaris ischemia in cases of placoid diseases or masking of the indocyanine green dye, as in multiple evanescent white dot syndrome. In addition, OCTA can depict neovascularization in granulomatous disease of the retina or choroid not previously depicted with previous imaging methods. While OCTA provides several advancements in the imaging, management and prognosis of uveitis diseases, we emphasize that further studies are required to fully understand its application to these conditions.

Choroidal metastases: origin, features, and therapy.

The choroid is the most common ocular site for metastatic disease, owing to abundant vascular supply. The primary cancers that most commonly lead to choroidal metastases include breast cancer (40-47%) and lung cancer (21-29%). Bilateral, multifocal metastases are most often secondary to breast cancer, whereas unilateral, unifocal metastasis are more commonly found with lung cancer. The treatment of choroidal metastasis depends on the systemic status of the patient and number, location, and laterality of the choroidal tumors. Treatment options include observation in patients with poor systemic status or those with resolved or asymptomatic disease; systemic chemotherapy, immunotherapy, hormone therapy, or whole eye radiotherapy if the metastases are active, multifocal and bilateral; plaque radiotherapy, transpupillary radiotherapy, or photodynamic therapy for active, solitary metastasis; and enucleation for those with blind painful eye. A database search was performed on PubMed, using the terms "choroidal metastasis," or "choroidal metastases," in combination with terms such as "treatment," "features," or "diagnosis." Relevant articles were extracted and reviewed.