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Purpose: To report a rare case of a conjunctival blue nevus in a child. Observations: A 10-year-old girl underwent an excisional biopsy for an atypical growing melanocytic conjunctival lesion. The diagnosis of a conjunctival blue nevus was confirmed on histopathology. We describe the histopathology and the anterior segment optical coherence tomography features of a blue nevus in a 10-year-old child along with a review of literature. Conclusion and importance: Conjunctival blue nevus is rare and has rarely been reported in a child. Multimodal imaging may help document lesion progression. This condition should remain in the differential for a growing, pigmented conjunctival lesion.

Objective: Detection of diabetic retinopathy (DR) outside of specialized eye care settings is an important means of access to vision-preserving health maintenance. Remote interpretation of fundus photographs acquired in a primary care or other nonophthalmic setting in a store-and-forward manner is a predominant paradigm of teleophthalmology screening programs. Artificial intelligence (AI)-based image interpretation offers an alternative means of DR detection. IDx-DR (Digital Diagnostics Inc) is a Food and Drug Administration-authorized autonomous testing device for DR. We evaluated the diagnostic performance of IDx-DR compared with human-based teleophthalmology over 2 and a half years. Additionally, we evaluated an AI-human hybrid workflow that combines AI-system evaluation with human expert-based assessment for referable cases. Design: Prospective cohort study and retrospective analysis. Participants: Diabetic patients ≥ 18 years old without a prior DR diagnosis or DR examination in the past year presenting for routine DR screening in a primary care clinic. Methods: Macula-centered and optic nerve-centered fundus photographs were evaluated by an AI algorithm followed by consensus-based overreading by retina specialists at the Stanford Ophthalmic Reading Center. Detection of more-than-mild diabetic retinopathy (MTMDR) was compared with in-person examination by a retina specialist. Main Outcome Measures: Sensitivity, specificity, accuracy, positive predictive value, and gradability achieved by the AI algorithm and retina specialists. Results: The AI algorithm had higher sensitivity (95.5% sensitivity; 95% confidence interval [CI], 86.7%–100%) but lower specificity (60.3% specificity; 95% CI, 47.7%–72.9%) for detection of MTMDR compared with remote image interpretation by retina specialists (69.5% sensitivity; 95% CI, 50.7%–88.3%; 96.9% specificity; 95% CI, 93.5%–100%). Gradability of encounters was also lower for the AI algorithm (62.5%) compared with retina specialists (93.1%). A 2-step AI-human hybrid workflow in which the AI algorithm initially rendered an assessment followed by overread by a retina specialist of MTMDR-positive encounters resulted in a sensitivity of 95.5% (95% CI, 86.7%–100%) and a specificity of 98.2% (95% CI, 94.6%–100%). Similarly, a 2-step overread by retina specialists of AI-ungradable encounters improved gradability from 63.5% to 95.6% of encounters. Conclusions: Implementation of an AI-human hybrid teleophthalmology workflow may both decrease reliance on human specialist effort and improve diagnostic accuracy. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To report the unusual case of a previously stable choroidal nevus, closely followed for over 15 years, which underwent malignant transformation into small choroidal melanoma with massive extrascleral extension. Observations: A 67-year-old Caucasian female was referred to the Stanford Ocular Oncology Service with concern for malignant transformation of a previously stable choroidal nevus in her left eye. Her funduscopic examination demonstrated a dome-shaped choroidal lesion with overlying associated lipofuscin and subretinal fluid, consistent with a diagnosis of small choroidal melanoma. By B-scan ultrasonography, the lesion measured 8.0 × 6.0 mm in base and 2.1 mm in thickness. B-scan ultrasonography also disclosed an associated retroscleral mass, which appeared contiguous with the intraocular melanoma and was confirmed on subsequent orbital magnetic resonance imaging. A decision was made to proceed with enucleation. Under direct endoscopic visualization, the globe and extrascleral mass were fully isolated, mobilized, and removed in toto. At 24 months post-enucleation, the patient remains disease-free without evidence of systemic metastasis or local recurrence. Conclusions/importance: This case describes a small choroidal melanoma hiding massive extrascleral extension, underscoring the value of B-scan ultrasonography. This case also describes the unique management of choroidal melanoma with extrascleral extension using endoscopic enucleation. Performing enucleation under direct endoscopic visualization ensures complete resection and prevents inadvertent transection of the extrascleral component.

Purpose: To describe the efficacy and safety of brolucizumab (Beovu®, Novartis Pharmaceuticals) in a case of cystoid macular edema associated with radiation retinopathy as a result of iodine-125 plaque brachytherapy (PBT) for choroidal melanoma, resistant to treatment with other anti-vascular endothelial growth factor (VEGF) agents. Observations: A 67-year-old woman with choroidal melanoma in the right eye and best-corrected visual acuity (BCVA) of 20/20, underwent uncomplicated PBT. On post-operative month 7, the patient developed early onset radiation retinopathy. She failed to improve significantly with sub-tenon triamcinolone and 3 injections of intravitreal bevacizumab; BCVA was 20/200. Intravitreal brolucizumab was administered, and one month after, macular edema had resolved completely on optical coherence tomography, and BCVA improved to 20/50. At last follow up, 1 month after the third brolucizumab injection, BCVA was 20/60 and there was sustained resolution of intraretinal fluid. There were no signs of intraocular inflammation, progressive RR or optic neuropathy on exam or fluorescein angiography. Conclusions: This case suggests a positive effect of brolucizumab in the management of radiation retinopathy following PBT refractory to other anti-VEGF agents. However, one must consider the risk of severe vision loss associated with retinal vasculitis from use of brolucizumab.

Purpose: To describe a case of presumed bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with renal cell carcinoma (RCC) and provide an updated review of literature. Observations: A 58-year-old man, with a history of radical nephrectomy for RCC 8 years ago, presented with gradual diminution of vision. Based on multimodal imaging and detailed systemic evaluation, a diagnosis of presumed BDUMP and metastatic RCC was made. He was started on sunitinib malate as palliative chemotherapy. However, he refused plasmapheresis for BDUMP. The patient rapidly developed bilateral exudative retinal detachment. Subsequently, he progressed to bilateral neovascular glaucoma secondary to closed funnel retinal detachment. Eventually, he was lost to follow up after 13 months. Conclusions & Importance: BDUMP portends an underlying advanced systemic malignancy. Studies have not conclusively proven any definite treatment for BDUMP and survival is generally poor. Ocular side effects of palliative targeted chemotherapy for the primary malignancy, such as sunitinib, should be borne in mind.

Purpose: To describe the management of submacular hemorrhage (SMH), a vision threatening complication following transvitreal choroidal biopsy, with intravitreal tissue plasminogen activator (tPA) and pure perfluoropropane (C3F8) gas bubble injection. Observations: A 53 year old female with choroidal melanoma of the left eye underwent iodine-125 plaque brachytherapy placement and 27 gauge transvitreal fine needle aspiration choroidal biopsy for gene expression profiling. On postoperative day 2, large SMH was identified on dilated fundus examination. At the time of plaque brachytherapy removal, intravitreal tPA and pure C3F8 gas bubble injection with post operative positioning was also performed to attempt displacement of SMH. At postoperative month 1 following tPA and gas bubble displacement, the SMH was completely displaced inferotemporally outside of the macula and visual acuity improved from 20/70 at postoperative week 1 to 20/25 at postoperative month 1. Conclusions and importance: Subretinal hemorrhage can be a complication of transvitreal choroidal tumor biopsy but early detection and prompt treatment can result in good visual outcomes.

Purpose: To report the association of pembrolizumab, an immune checkpoint inhibitor (ICI), with giant cell arteritis (GCA) presenting as paracentral acute middle maculopathy (PAMM) secondary to retinal arterial occlusion. Observations: 86-year old male with history of treated choroidal melanoma now with metastatic uveal melanoma to the liver on pembrolizumab, an ICI, who presented with acute vision loss in the uninvolved left eye. Spectral domain optical coherence tomography showed band-like increased hyperreflectivity in the middle retinal layers at the level of the inner nuclear layer consistent with PAMM. Intravenous fluorescein angiogram demonstrated significant delay in filling of the superotemporal and inferotemporal arteries with nonperfusion of the temporal retina consistent with multiple branch retinal arterial occlusions. Work-up for GCA was performed and temporal artery biopsy showed healed arteritis. Conclusions and Importance: Pembrolizumab can cause ocular and life-threatening systemic adverse effects and as use of ICIs has increased, it is important to be aware of these associations. There should be a low threshold for GCA work up in patients on ICI therapy who present with acute vision loss and evidence of retinal occlusive disease with or without classic GCA systemic symptoms.

Summary: Antimicrobial peptides (AMPs) are the body’s natural innate immune defense against a spectrum of pathogens and can also modulate cell proliferation, chemotaxis, angiogenesis, wound healing, and immune cell activity. Harnessing these diverse functions for prophylactic use is contingent upon understanding the regulatory mechanisms governing their unconventional secretion from cells. Analysis of the secretion of S100A7 (Psoriasin), an abundant AMP stored in differentiated keratinocytes of the skin, has revealed an unexpected biphasic secretory response to bacterial exposure. The core components regulating S100A7 secretion are NFκB/p38MAPK, caspase-1, and interleukin (IL)-1α. The initial activation of this core machinery is mediated by Toll-like receptor signaling, whereas the chronic response is mediated by Caspase-8 downregulation. Interestingly, there is a concomitant downregulation of Caspase-8 in inflammatory skin diseases wherein S100A7 is constitutively released. These results highlight the potential of targeting these components to control the release of AMPs from the skin in both homeostatic and disease conditions. : The global explosion of antibiotic-resistant microorganisms has spurred interest in alternative strategies to combat these “superbugs.” Antimicrobial peptides (AMPs) have emerged as a promising solution. Bhatt et al. show downregulation of epidermal caspase-8 can mediate sustained release of AMPs from the skin and provide an effective defense against infection. keywords: caspase, antimicrobial peptides, skin, TLR, IL-1, NFkB, psoriasis, antibiotic resistance

Trans-radial intervention increases patient comfort and reduces vascular complications. Trans-radial access has become the preferred choice of patients and cardiologists. Radial artery spasm is commonly encountered during procedure and it depends upon factors like artery anatomy, built of the patient, procedure variables. We report a case of radial artery spasm leading to avulsion in a 69-year old short Asian female during coronary angiogram, which was managed successfully by conservative measures. A brief note of various management procedures like drugs and device are mentioned.

ABSTRACT: Objective: H syndrome is a monogenic systemic inherited form of histiocytosis, with characteristic cutaneous findings accompanying systemic manifestations. The major common endocrine manifestations include hypogonadism, short stature, and diabetes mellitus with characteristic genodermatosis and lead to the diagnosis. Here, we report a rare case of H-syndrome, an autosomal recessive non-autoimmune disorder in a 19-year-old woman who presented with short stature, diabetes mellitus, and hypogonadism associated with characteristic hyperpigmentation and hypertrichosis. The molecular diagnosis was established utilizing next-generation sequencing (NGS) technology.Methods: We describe the clinical spectrum of H syndrome with endocrine and non endocrine multisystem involvement. The solute carrier family 29 (nucleoside transporters), member 3 (SLC29A3) gene was screened for molecular diagnosis utilizing NGS based mutational analysis.Results: H syndrome is caused by a mutation in the SLC29A3 gene, which encodes human equilibrative nucleoside transporter 3. A 19-year-old woman was diagnosed to have diabetes mellitus at the age of 6 years. Her clinical phenotype included short stature, hypogonadotropic hypogonadism, hearing loss, hypothyroidism, heart involvement, and hyperpigmentation with hypertrichosis. Her erythrocyte sedimentation rate and C-reactive protein levels were elevated. A clinical diagnosis of H syndrome was considered, and utilizing an NGS-based approach, we identified a reported homozygous missense mutation (c.400C>T, p.Arg134Cys) in the SLC29A3 gene, which was confirmed by Sanger sequencing.Conclusion: The characteristic pigmentary hypertrichosis and elevated inflammatory markers differentiate H syndrome from mitochondrial disorders and Turners syndrome with similar endocrine manifestations. With its multiplexing option, NGS offers a rapid and robust platform for molecular diagnosis at an affordable cost.Abbreviations: hENT3 = human equilibrative nucleoside transporter 3 NGS = next-generation sequencing SLC29A3 = solute carrier family 29 (nucleoside transporter), member 3

Purpose: Conversion to neovascular disease in patients with non-neovascular age-related macular degeneration (AMD) initiated on direct oral anticoagulants (DOAC) compared to matched patients treated with warfarin., Design: Retrospective cohort study., Subjects, Participants, And/or Controls: The study included 20,300 patients and 13,387 patients with non-neovascular AMD initiated on DOACs or warfarin, respectively, before propensity score matching (PSM)., Methods, Intervention, or Testing: TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with non-neovascular AMD stratified by treatment with DOACs or warfarin with at least six months of follow-up. Propensity score matching was performed to control for baseline demographics and medical comorbidities., Main Outcome Measures: Relative risk (RR) of developing neovascular AMD, macular hemorrhage (MH), vitreous hemorrhage (VH), and requiring an ocular intervention (intravitreal anti-vascular endothelial growth factor (VEGF) therapy or pars plana vitrectomy (PPV)) within six months and one year. Patients with chronic atrial fibrillation (AF) on anticoagulation were separately evaluated for the same measures within 5 years after initiating therapy., Results: Treatment with warfarin was associated with higher risk of developing neovascular AMD at six months (RR,1.24, 95% CI, 1.12 - 1.39; P<.001) and one year (RR, 1.26, 95% CI, 1.14 - 1.40; P<.001) when compared to matched patients treated with DOACs. There was an increased risk of requiring intravitreal anti-VEGF therapy (6 months: RR, 1.30; 95% CI, 1.13-1.49; P<.001; 1 year: RR, 1.31, 95% CI, 0.72 - 2.05; P<.001) and PPV (6 months: RR, 1.16; 95% CI, 1.16-3.94; P = .01; 1 year: RR, 2.29, 95% CI, 1.30 - 4.05; P=.003). Among patients with AMD and AF treated with warfarin, there was an increased risk of ocular complications (neovascular AMD: RR, 1.25; 95% CI, 1.14-1.38; P<.001; MH: RR, 1.86; 95% CI, 1.47-2.35; P<.001; VH: RR, 2.22; 95% CI, 1.51-3.26; P<.001) and need for intravitreal anti-VEGF therapy (RR, 1.34; 95% CI, 1.18-1.52; P<.001) over an extended 5-year period. There was no significant difference in the development of major systemic hemorrhagic events between the two cohorts over five years., Conclusions: Patients with non-neovascular AMD treated with warfarin were more likely to develop neovascular disease and require ocular intervention for hemorrhagic complications when compared to matched patients initiated on DOACs., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) and risk of postoperative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair., Design: Retrospective, population-based cohort study., Participants: Patients aged ≥ 18 years who underwent initial retinal detachment (RD) repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology [CPT] 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003, to March 1, 2023., Methods: A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Classification of Diseases, 10 th Revision (ICD-10) codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2) and CPT codes for secondary surgery including complex RD repair (67113) were determined. Patients with proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) were used to match for age, sex, and race., Main Outcome Measures: Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in the KHF cohort versus the non-KHF cohort., Results: Among patients with CPT 67108, 1061 in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (standard deviation) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (P < 0.001, odds ratio [OR], 3.2; 95% confidence interval [CI], 2.13-4.71). A total of 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (P = 0.008; OR, 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF cohort than in the non-KHF cohort (9.0% vs 4.2%, P < 0.01; OR, 2.28; 95% CI, 1.64-3.16)., Conclusions: A dermatologic history of KHF may be a risk factor for PVR after RD repair., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Anti-vascular endothelial growth factor (VEGF) medications for intraocular use are a major and increasing cost, and biosimilars may be a means of reducing the high cost of many biologic medications. However, a bevacizumab biosimilar, which is currently pending Food and Drug Administration (FDA) approval (bevacizumab-vikg), paradoxically may increase the cost burden of intravitreal anti-VEGF agents, because off-label repackaged drugs may no longer be allowed per the Drug Quality and Security Act (DQSA). We aimed to investigate the potential impact of biosimilars on costs in the United States., Design: Cost analysis of anti-VEGF medications., Participants: Medicare data from October 2022 and previously published market share data from 2019., Methods: Average sales prices (ASPs) of ranibizumab, aflibercept, and bevacizumab were calculated from Medicare allowable payments. The ASPs of biosimilars were calculated from wholesale acquisition costs from a representative distributor. The cost of an intraocular bevacizumab formulation is modeled at $500/1.25-mg dose and $900/1.25-mg dose., Main Outcome Measures: Costs of anti-VEGF drugs to Medicare Part B and patients., Results: If an intraocular bevacizumab biosimilar were to be priced at $500, costs to Medicare would increase by $457 million from $3.01 billion to $3.47 billion (15.2% increase). Patient responsibility would increase by $117 million from $768 million to $884 million. Similarly, if intraocular bevacizumab were priced at $900, Medicare costs would increase by $897 million to $3.91 billion (29.8% increase), and patient responsibility would increase by $229 million to $997 million. If bevacizumab were $500/dose, switching all patients currently receiving ranibizumab or aflibercept to respective biosimilars would compensate for only 28.8% of the increased cost. Current prices of ranibizumab and aflibercept biosimilars would have to decrease by an aggregate of 15.7% to $616.80/injection, $1027.97/injection, and $1436.88/injection for ranibizumab 0.3 mg, ranibizumab 0.5 mg, and aflibercept, respectively., Conclusions: An FDA-approved bevacizumab biosimilar for ophthalmic use could increase costs to the health care system and patients, raising concerns for access. This increase would not be offset by ranibizumab and aflibercept biosimilar use at current prices. These data support the need for an exemption of section 503B of the DQSA and continued use of repackaged off-label bevacizumab., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. All rights reserved.)

Purpose: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME)., Methods: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist., Results: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2)., Conclusions: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To estimate temporal trends in total and out-of-pocket (OOP) expenditures for ophthalmic prescription medications among adults in the United States., Design: Retrospective, longitudinal cohort study., Participants: Participants in the 2007 through 2016 Medical Expenditure Panel Survey (MEPS) 18 years of age or older. The MEPS is a nationally representative survey of the noninstitutionalized, civilian United States population., Methods: We estimated trends in national and per capita annual ophthalmic prescription expenditures by pooling data into 2-year cycles and using weighted linear regressions. We also identified characteristics associated with greater total or OOP expenditures with multivariate weighted linear regression. Costs were adjusted to 2016 United States dollars using the gross domestic product price index., Main Outcome Measures: Trends in total and OOP annual expenditures for ophthalmic medications from 2007 through 2016 as well as factors associated with greater expenditures., Results: From 2007 through 2016, 9989 MEPS participants (4.2%) reported ophthalmic medication prescription use. Annual ophthalmic medication use increased from 10.0 to 12.2 million individuals from 2007 and 2008 through 2015 and 2016. In this same period, national expenditures for ophthalmic medications increased from $3.39 billion to $6.08 billion and OOP expenditures decreased from $1.34 to $1.18 billion. Per capita expenditure increased from $338.72 to $499.42 (P < 0.001), and per capita OOP expenditure decreased from $133.48 to $96.67 (P < 0.001) from 2007 and 2008 through 2015 and 2016, respectively. From 2015 through 2016, dry eye (29.5%) and glaucoma (42.7%) medications accounted for 72.2% of all ophthalmic medication expenditures. Patients who were older than 65 years (P < 0.001), uninsured (P < 0.001), and visually impaired (P < 0.001) were significantly more likely to have greater OOP spending on ophthalmic medications., Conclusions: Total ophthalmic medication expenditure in the United States increased significantly over the last decade, whereas OOP expenses decreased. Increases in coverage, copayment assistance, and use of expensive brand drugs may be contributing to these trends. Policy makers and physicians should be aware that rising overall drug expenditures ultimately may increase indirect costs to the patient and offset a decline in OOP prescription drug spending., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the effect of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents on immediate and long-term intraocular pressure (IOP) elevation and glaucoma., Methods: Literature searches of the PubMed and Cochrane databases, last conducted in April 2018, yielded 253 unique citations. Of these, 41 met the inclusion criteria and were rated according to the strength of evidence. Two articles were rated level I, 17 were rated level II, and 15 were rated level III; an additional 7 were excluded because of poor study design and lack of relevance to the topic under evaluation., Results: The studies that reported on short-term IOP elevation (i.e., between 0 and 60 minutes) showed that an immediate increase in IOP is seen in all patients when measured between 0 and 30 minutes of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; 7 studies reported that between 4% and 15% of patients developed sustained elevation of IOP at 9 to 24 months after injection, whereas 6 studies found no long-term change in IOP from 1 to 36 months after injection. Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection. Data were mixed on the relationship between IOP increase and the type of intravitreal injection, number of intravitreal injections, preexisting glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment., Conclusions: Intravitreal injection of anti-VEGF agents results in an immediate and transient increase in IOP. A long-term increase in IOP also may be seen, and further studies are needed to determine at-risk populations. Although there is some suggestion in the literature, there is currently insufficient data to determine the impact of intravitreal anti-VEGF injections on glaucoma progression. Although pretreatment with glaucoma medications, performing anterior chamber paracentesis, or increasing the interval between injections may reduce the impact of transient IOP elevation, the clinical significance and associated risks of these interventions are unknown., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Gene expression profile (GEP) testing segregates uveal melanoma (UM) into 2 main prognostic classes. It is unknown if a greater tumor regression response after iodine 125 (I 125 ) brachytherapy correlates with class 2 GEP status. The purpose of this study was to determine whether there is a significant relationship between the rate of UM height regression and GEP classification testing after I 125 plaque brachytherapy., Design: Multicenter, retrospective cohort study., Participants: Adult UM patients treated with I 125 plaque brachytherapy who had concurrent tumor biopsy at the time of surgery with a GEP test result from January 1, 2010 through June 30, 2014., Methods: Baseline clinical data and GEP class assignments were obtained. The ultrasonographic tumor height was recorded at baseline and at 3, 6, 9, and 12 months and at the most recent final follow-up visits. Subanalysis of paired cases based on pretreatment ultrasound height was performed. Statistical analysis was performed using Wilcoxon rank-sum tests, the Fisher exact test, and Kaplan-Meier analysis., Main Outcome Measures: Percentage change in tumor height from baseline., Results: A total of 353 patients were included in the study. Median follow-up was 2.1 years (range, 0.5-5.3 years). Gene expression profile status was class 1 in 247 tumors (70%) and class 2 in 106 tumors (30%). Increased patient age, larger tumor dimensions, and greater tumor thickness were associated with class 2 GEP status (P = 0.006, P < 0.001, and P < 0.001, respectively). The percentage reduction in tumor height from baseline was significantly greater in class 1 than class 2 tumors at 3 months (17.5% vs. 11.8%; P = 0.007) and 6 months (26.8% vs. 17.1%; P = 0.007), respectively, but there was no significant difference in reduction between class 1 and 2 tumors at 9 months (P = 0.26) and 12 months (P = 0.57) after treatment. Class 1A and 1B tumors showed similar reduction compared with class 2 tumors (P < 0.05)., Conclusions: Class 1 UM tumors tend to regress more rapidly than class 2 tumors in the first 6 months after plaque radiotherapy. Class 1A and 1B tumors regress at similar rates after plaque radiotherapy., (Copyright © 2017 American Academy of Ophthalmology. All rights reserved.)

Purpose: To evaluate the available evidence on the ocular safety and efficacy of current therapeutic alternatives for the management of macular edema (ME) secondary to branch retinal vein occlusion (BRVO)., Methods: Literature searches were last conducted on January 31, 2017, in PubMed with no date restrictions and limited to articles published in English, and in the Cochrane Database without language limitations. The searches yielded 321 citations, of which 109 were reviewed in full text and 27 were deemed appropriate for inclusion in this assessment. The panel methodologist assigned ratings to the selected studies according to the level of evidence., Results: Level I evidence was identified in 10 articles that addressed anti-vascular endothelial growth factor (VEGF) pharmacotherapies for ME, including intravitreal bevacizumab (5), aflibercept (2), and ranibizumab (4). Level I evidence was identified in 6 studies that examined intravitreal corticosteroids, including triamcinolone (4) and the dexamethasone implant (2). Level I evidence also was available for the role of macular grid laser photocoagulation (7) and scatter peripheral laser surgery (1). The inclusion of level II and level III studies was limited given the preponderance of level I studies. The number of studies on combination therapy is limited., Conclusions: Current level I evidence suggests that intravitreal pharmacotherapy with anti-VEGF agents is effective and safe for ME secondary to BRVO. Prolonged delay in treatment is associated with less improvement in visual acuity (VA). Level I evidence also indicates that intravitreal corticosteroids are effective and safe for the management of ME associated with BRVO; however, corticosteroids are associated with increased potential ocular side effects (e.g., elevated intraocular pressure, cataracts). Laser photocoagulation remains a safe and effective therapy, but VA results lag behind the results for anti-VEGF therapies., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report differences in visual acuities among patients with Coats' disease who sought treatment at a tertiary care university-based practice., Design: Single-center retrospective cohort study., Participants: Patients with Coats' disease diagnosed clinically, angiographically, or both from 1995 through 2015., Methods: Patients were divided into 2 groups based on date of presentation: decade 1 (1995-2005) and decade 2 (2006-2015)., Main Outcome Measures: Visual acuity (VA)., Results: Thirty-nine eyes of 39 patients were included with 19 eyes presenting in decade 1 and 20 eyes presenting in decade 2. Three patients demonstrated bilateral disease, but only the worse eye was included for analysis. Forty-seven percent of eyes in decade 1 demonstrated advanced stages of disease (stage 3B or worse) compared with 20% of eyes in decade 2. There was a trend for the mean initial presenting VA (±standard deviation) for decade 1 eyes to be worse (2.05±1.29 logarithm of the minimum angle of resolution [logMAR]) than for decade 2 eyes (1.45±0.99 logMAR; P = 0.1). From initial to final follow-up visit, mean VA also worsened for decade 1 eyes (P = 0.03), but remained stable for decade 2 eyes (P = 1.0). At the end of follow-up, there was a trend for mean VA for decade 1 eyes (2.28±1.17 logMAR) to be worse than for decade 2 eyes (1.60±1.15 logMAR; P = 0.07). Eight eyes were observed initially in decade 1 compared with 1 eye in decade 2, and only 1 of the observed eyes (in decade 2) developed painful glaucoma requiring enucleation. Decade 2 eyes had a higher average number of procedures per eye (6.5±4.9) compared with decade 1 eyes (1.4±1.7; P < 0.001)., Conclusions: The earlier presentation of disease in decade 2 suggests improvements in disease detection over time. Furthermore, there was a trend for eyes to have better final VA in this decade. This is due to a combination of factors, including earlier presentation of disease, fewer eyes being observed without treatment, and eyes, when treated, receiving a higher number of procedures., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN)., Methods: Literature searches of the PubMed and Cochrane Library databases were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective., Results: Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear., Conclusions: Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis of ARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk)., Design: Prospective, multicenter study., Participants: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers., Testing: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status., Main Outcome Measures: Patients were managed for their primary tumor and monitored for metastasis., Results: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status., Conclusions: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To identify clinical factors and microbiological assays that facilitate a rapid diagnosis of Nocardia keratitis, scleritis, and endophthalmitis, and to determine optimal medical and surgical management strategies., Design: Retrospective, consecutive case series., Participants: A total of 111 cases of keratitis, 11 cases of scleritis, and 16 cases of endophthalmitis, all culture-proven Nocardia infections, were identified between January 1999 and January 2010., Intervention: The keratitis cases underwent intensive medical management, and the scleritis and endophthalmitis cases required concurrent surgical intervention for disease control. Corneal and scleral scrapings, as well as undiluted vitreous sample, were submitted for microbiologic evaluation (direct smear and culture)., Main Outcome Measures: Historical points, clinical findings, and microbiologic assays that facilitated a prompt Nocardia diagnosis were identified, and management choices were examined for correlation with final acuity., Results: Ocular exposure to soil or plant matter was a common historical point in cases of Nocardia keratitis (48%) and scleritis (45%), respectively. Nocardia keratitis often (38.7%) presented with "wreath"-shaped anterior stromal infiltrate or infiltrate interspersed with elevated, pinhead-sized, chalky lesions. Most patients with scleritis (63.4%) presented with nodular lesions demonstrating pointed abscesses. Nocardia endophthalmitis typically (75%) presented with endoexudates or nodular exudates surrounding the pupillary border. Gram stain and 1% acid-fast stain enabled prompt diagnosis of Nocardia in 64% and 63% of keratitis cases and 45% and 63% of scleritis cases, respectively. Direct smear was usually not revealing in cases of Nocardia endophthalmitis. Isolates from Nocardia keratitis, scleritis, and endophthalmitis demonstrated 97%, 100%, and 90% susceptibility to amikacin, respectively. Nocardia keratitis resolved with medical therapy alone in 82% of cases. Younger age and better initial acuity correlated with improved final acuity in keratitis cases. Outcomes were poor after Nocardia scleritis and endophthalmitis., Conclusions: Early appropriate treatment often results in visual recovery in eyes with Nocardia keratitis. Despite aggressive and prompt surgical intervention, the prognosis for Nocardia scleritis and endophthalmitis is more guarded. Nocardia isolated from ocular infections demonstrate high levels of susceptibility to amikacin., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To measure the change in vision and visual outcomes at 12 months after macular translocation with 360 degrees retinectomy (MT360) and silicone oil tamponade in patients with bilateral vision loss resulting from subfoveal choroidal neovascular membranes in age-related macular degeneration (AMD)., Design: A prospective, interventional, consecutive, noncomparative case series., Participants: Sixty-four patients with bilateral vision loss resulting from neovascular AMD., Methods: Eligible patients had AMD with subfoveal choroidal neovascularization in the operative eye and a maximum of 6 months of central vision loss. Preoperative and 12-month postoperative evaluations included standardized testing of near and distance acuity and reading speed. Patients underwent MT360 with silicone oil tamponade, followed 2 months later by extraocular muscle surgery and silicone oil removal., Main Outcome Measures: Change in distance acuity, near acuity, and reading speed at 12 months after MT360 compared with those values before surgery., Results: Sixty-one patients were followed up for 12 months. All eyes were translocated successfully. Median distance acuity letter score improved from 62 letters (Snellen equivalent of approximately 20/125) before surgery to 69 letters (approximately 20/80) by 12 months after surgery (P = 0.03). Median near acuity improved from 0.70 logarithm of the minimum angle of resolution (logMAR) units (approximately 20/100) before surgery to 0.44 logMAR units (approximately 20/55) at 12 months (P<0.001). Median reading speed improved from 71 words per minute (wpm) before surgery to 105 wpm at 12 months after surgery (P<0.001). At 12 months, distance acuity improved by 1 or more lines in 32 patients (52%). In patients with either preoperative distance or near acuity of 20/80 or better, 74% and 95% of patients, respectively, remained in this range of acuity. In patients with either preoperative distance or near acuity of worse than 20/80, 40% and 48% of patients, respectively, improved to 20/80 or better. Postoperative retinal detachment developed in 5 patients (8%), with the macula involved in 2 patients, and all retinas were reattached successfully., Conclusions: Macular translocation with 360 degrees retinectomy with silicone oil tamponade is effective in significantly improving visual function in patients with neovascular AMD, as demonstrated by the improvement in distance and near acuity and reading speed at 12 months after surgery in these patients. Although this is a complex surgical intervention, patients with preoperative visual acuity of 20/80 or better at near or distance are highly likely to retain the 20/80 or better acuity at 12 months after surgery. Macular translocation with 360 degrees retinectomy is an effective treatment option for patients with vision loss in their second eye resulting from neovascular AMD.

Purpose: To determine the yield of diagnostic pars plana vitrectomy in eyes with suspected posterior segment inflammation or malignancy when clinical examination and systemic laboratory testing did not yield a specific diagnosis., Design: Non-comparative interventional case series, Participants: Eighty-seven consecutive patients (90 eyes) who underwent diagnostic pars plana vitrectomy from 1989 through 1999., Interventions: Vitreous samples were analyzed in a directed manner based on the preoperative clinical examination and systemic laboratory testing., Main Outcome Measures: Diagnosis from each test performed on the vitreous samples., Results: Diagnostic vitrectomy was performed alone in 6 eyes (7%) and as part of a therapeutic procedure in the remaining 84 eyes. The diagnostic tests performed most frequently included cytopathology (83%), microbiologic culture and sensitivity (43%), polymerase chain reaction (PCR) (36%), and intraocular antibody levels for T. canis (14%). Of these, intraocular antibody testing and PCR had the highest positive yield, 46% and 39%, respectively. Overall, directed vitreous analysis identified a specific cause in 35 eyes (39%). Of the 65 cases in which an underlying infection was suspected preoperatively, the procedure yielded a specific diagnosis in 27 (42%). When intraocular malignancy was considered preoperatively (71 eyes), a diagnosis of intraocular lymphoma was obtained in seven (10%). This difference between these diagnostic yields was significant (P = 0.02, Fisher's exact test)., Conclusions: Diagnostic vitrectomy with directed vitreous fluid analysis yields a specific cause and guides subsequent therapy in a high percentage of cases. This procedure is a valuable adjunct in cases that cannot be diagnosed by less invasive methods.