Retinal injury from a laser skin resurfacing device during medical tourism: a public health concern.

BACKGROUND: Laser skin resurfacing is a popular cosmetic procedure for noninvasive skin rejuvenation. Since health insurance plans often do not cover these types of procedures, patients often pay out of pocket. Consequently, there is an incentive to go abroad, where prices are more affordable. However, practitioners in destination countries may lack rigorous training on laser safety, regulatory oversight, or licensing, especially on devices used for "cosmetic" procedures. In certain cases, this can lead to tragic outcomes, especially when underqualified practitioners operate medical-grade laser devices. CASE PRESENTATION: A 29-year-old woman suffered a retinal burn from a handheld Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser pulse device used to perform skin resurfacing treatment at a medical spa in Vietnam. The patient was not adequately informed about the potential risk to her vision and was not provided with any eye protection. A momentary, unintended laser exposure to the patient's right eye led to irreversible vision loss due to a macular burn. This incident caused immediate pain, followed by the sudden appearance of floaters, along with a retinal and vitreous hemorrhage. Despite treatment with off-label bevacizumab for the development of a choroidal neovascular membrane, vision remained at the level of counting fingers because of the presence of the macular scar. CONCLUSION: When utilizing laser-based devices, it is crucial to employ safety measures, such as the wearing of safety goggles or the use of eye shields to protect ocular tissues from potential damage. The growing availability of cosmetic laser devices presents a substantial public health risk, because numerous operators lack adequate training in essential safety standards, or they neglect to follow them. Furthermore, patients seeking services abroad are subject to the regulatory practices of the destination country, which may not always enforce the requisite safety standards. Further research is needed to determine regional and global incidence of laser-related injuries to help direct educational and regulatory efforts.

Advancing Inclusive Research (AIR) Site Alliance: Facilitating the inclusion of historically underrepresented people in oncology and ophthalmology clinical research.

BACKGROUND: The Advancing Inclusive Research (AIR) Site Alliance is composed of clinical research centers that partner with Genentech, a biotechnology company, to advance the representation of diverse patient populations in its oncology and ophthalmology clinical trials, test recruitment, and retention approaches and establish best practices to leverage across the industry to achieve health equity. METHODS: Through a data-driven selection process, Genentech identified 6 oncology and 3 ophthalmology partners that focus on reaching historically underrepresented patients in clinical trials and worked collaboratively to share knowledge and explore original ways of increasing clinical study access for every patient, including sites co-creation of a Protocol Entry Criteria Guideline with inclusion principles. RESULTS: For patients, three publicly available educational videos about clinical trials were created in multiple languages. The AIR Site Alliance has also defined invoiceable services for sites to enhance patient support; this has been built into the new study budget templates for sustainability. For healthcare professionals (HCPs), the first-of-its-kind AIR Educational Program was developed to focus on identifying and addressing bias and engaging historically underrepresented patient populations in trials. The sites also co-created videos for HCPs and patients on why advancing inclusive research matters. Over 16 regional health equity symposia have been delivered for patients, HCPs, and community leaders. CONCLUSIONS: This AIR Site Alliance is a model for other site alliances, including Kenya, South Africa, the United Kingdom, and Canada. Such alliances will build a robust and sustainable research ecosystem that includes diverse patient groups and encourages change across the healthcare system.

Adenosine-Induced Atrial Fibrillation During Coronary Angiography and Fractional Flow Reserve Procedures.

A woman in her sixties presented with a history of progressive shortness of breath, palpitations, and feeling of chest heaviness for the last eight months. To rule out underlying obstructive coronary artery disease, an invasive cardiac catheterization was planned. To assess the hemodynamic significance of the lesion, resting full cycle ratio (RFR) and fractional flow reserve (FFR) values were measured. During this procedure, almost immediately after starting IV adenosine infusion, the patient went into atrial fibrillation which was reversed by IV aminophylline. Awareness of this uncommon effect of adenosine on the cardiac electrical pathways merits knowledge and a thorough follow-up testing of these patients is justified.

Ziv-aflibercept for Better Regulating Neovascular Age-Related Macular Degeneration (ZEBRA): A Prospective, Randomized Trial.

OBJECTIVE: The purpose of this study is to determine if ziv-aflibercept is a safe and effective maintenance drug for nAMD. STUDY DESIGN AND METHODS: This is a randomized, prospective, single-blinded trial. Inclusion criteria were active nAMD, prior anti-VEGF treatment, and BCVA ≤20/200. The treatment group received ziv-aflibercept. The control group continued their existing anti-VEGF regimen. The main outcome measures were BCVA, CFT, and safety. RESULTS: Mean baseline BCVA was 1.58 ± 0.44 logMAR and 1.71 ± 0.39 logMAR in the control (n = 27) and treatment (n = 29) groups, respectively. After 24 months, the mean change in BCVA was 0.11 in the control group (equivalent to a loss of 5 ETDRS letters) and 0.01 logMAR in the treatment group (p = .48). Baseline CFT was 257 ± 33 µm and 247 ± 30 µm in the control and treatment groups, respectively, and after 24 months mean change in CFT was 26 µm and -5 µm (p = .24). There were no ocular or systemic adverse events during the study. CONCLUSION: Ziv-aflibercept is a safe and effective as a maintenance drug for patients with nAMD. It may represent a cost-effective alternative to aflibercept and second-line therapy for eye resistant bevacizumab or ranibizumab.

Successful Clinical Outcome of Vancomycin-induced Hemorrhagic Occlusive Retinal Vasculitis.

We present a case of a patient that experienced severe hemorrhagic occlusive retinal vasculitis secondary to injection of 1.0 mg/0.1 ml of intracameral vancomycin for endophthalmitis prophylaxis after an uneventful cataract surgery. The case is especially unique in that our patient ended up maintaining 20/25 vision with an ocular disease that is typically visually threatening. This may be due to the aggressive administration of periocular and oral steroids combined with scheduled anti-VEGF injections that were later transitioned into a treat and extend regimen.

Retinal vascular manifestations of obstructive sleep apnea.

PURPOSE OF REVIEW: The aim of this article is to summarize up-to-date research on the effects of obstructive sleep apnea (OSA) on retinal vascular conditions. RECENT FINDINGS: OSA is associated with the development of diabetic retinopathy, retinal vein occlusion, and central serous chorioretinopathy. The severity of OSA and biomarkers such as the apnea-hypopnea index (AHI) correlate with the severity of retinal disease. Dysregulation of circadian locomotor output cycles kaput (CLOCK) genes that govern circadian rhythm is associated with development of proliferative retinal disease. SUMMARY: OSA and retinal vascular disease have a high cost burden on the healthcare system. OSA creates systemic changes and hypoxic conditions that may incite or exacerbate retinal vascular diseases. Retinal changes may be the first clinical manifestation of otherwise undiagnosed OSA, so it is important to refer patients with new-onset retinal vascular disease for appropriate sleep testing.

SAFETY OF CONSECUTIVE SAME-DAY BILATERAL INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX).

PURPOSE: The objective of this study was to evaluate patient safety and tolerance of consecutive bilateral intravitreal dexamethasone (Ozurdex) injections during a single visit for the treatment of cystoid macular edema secondary to retinal vein occlusion, diabetic macular edema, or noninfectious posterior uveitis. METHODS: This was a retrospective single-center institutional review board-approved study from March 1, 2013, through August 1, 2016. All patients had a complete ophthalmologic examination and optical coherence tomography imaging. Bilateral intravitreal dexamethasone (Ozurdex) injection was performed according to standard sterile procedure. Twelve patients (24 eyes) were included in the study. RESULTS: A total of 48 injections were administered to 24 eyes of 12 patients that qualified for the study. Patients received intravitreal dexamethasone (Ozurdex) injections for treatment of diabetic macular edema (10 patients), retinal vein occlusion (1 patient), or noninfectious posterior uveitis (1 patient). There were no complications. CONCLUSION: Consecutive same-day bilateral intravitreal dexamethasone (Ozurdex) is safe and well tolerated. There were no significant complications, and patients preferred continuing bilateral implantation after their initial trial. Same-day treatment may optimize efficiency and decrease patient visits and ultimate treatment burden without compromising patient safety or clinical efficacy.

Intravitreal Ziv-Aflibercept: A Comprehensive Review.

Background: Age-related macular degeneration is the leading cause of blindness in adults over the age of 50 in the United States of America. Neovascular age-related macular degeneration (nAMD) is sight-threatening, but can be treated by three currently utilized, intravitreally administered drugs: aflibercept, bevacizumab, and ranibizumab. Ziv-aflibercept is an analogue of aflibercept, containing the same active molecule in a different buffer solution, and its recent availability has prompted numerous pre-clinical and clinical trials addressing its viability for intraocular use, summarized herein. Results: Trial outcomes demonstrate that ziv-aflibercept has a similar safety profile to other indicated drugs with effective maintenance or improvement of best-corrected visual acuity (BCVA) and reduction of retinal fluid or central foveal thickness (CFT). Clinical trials of ziv-aflibercept in other neovascular disorders such as diabetic macular edema (DME) and retinal vein occlusion (RVO) have shown similar results. Conclusion: Further prospective, randomized studies of ziv-aflibercept are needed, particularly in eyes with nAMD.

Updated Cost-Effectiveness of Intravitreal Ocriplasmin for Vitreomacular Adhesion and Macular Hole.

BACKGROUND AND OBJECTIVE: The purpose of this study is to provide an updated assessment of cost-efficacy of intravitreal ocriplasmin (IVO) for vitreomacular adhesion (VMA) and macular holes (MH). PATIENTS AND METHODS: This was a single-center, multiple-physician, institutional review board-approved, retrospective, 15-month cost-effectiveness analysis study (January 2015 to April 2016). Clinical charts and billing records of 247 patients with VMA and MH were reviewed. Patients were divided into group 1 (VMA and MH treated by pars plana vitrectomy [PPV]), group 2 (VMA and MH treated by IVO), and group 3 (VMA treated by IVO). Success rates of interventions in each group were compared, including cost-effectiveness, cost per line-year, and cost per quality-adjusted life-year (QALY). RESULTS: Success rates for initial intervention were 98% in group 1, 55.6% in group 2, and 67.7% in group 3. Cost of PPV at our institution was $6,538.00 and cost of IVO (2016) was $3,480.00. Using a cohort-based computer Markov model, the treatment decision tree demonstrated group 1 was less cost-effective, with cost per line of $2,654.39, cost per line-year saved of $185.62, and cost per QALY of $6,187.00. Group 2 was cost-effective with cost per line of $2,456.25, cost per line-year saved of $171.77, and cost per QALY of $5,726.00. The difference in cost-effectiveness showed IVO was more cost-effective than PPV, with a difference in cost per line of $198.14, cost per line-year saved of $13.85, and cost per QALY of $461.00. CONCLUSIONS: IVO is a more cost-effective intervention than vitrectomy for the treatment of VMA and MH in the setting of judicious use in appropriate patients. The success rate of IVO in our patient population was greater than currently published rates and most certainly impacted probability of cost-efficacy. Further research targeting optimizing IVO success rate is needed. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e240-e248.].

Access to Ophthalmologists in States Where Optometrists Have Expanded Scope of Practice.

Importance: As the United States considers how to best structure its health care services, specialty care availability is receiving increased focus. This study assesses whether patients lack reasonable access to ophthalmologists in states where optometrists have been granted expanded scope of practice. Objective: To determine the estimated travel time (ETT) to the nearest ophthalmologist office for persons residing in states that have expanded scope of practice for optometrists, and to quantify ETT to the nearest ophthalmologist for Medicare beneficiaries who received surgical care from optometrists in those states between 2008 and 2014. Design, Setting, and Participants: This study used data from the 2010 US census, a 2016 American Academy of Ophthalmology member database, and a data set of claims data for a random sample of 20% of beneficiaries enrolled in Medicare nationwide from 2008 to 2014 (n=14 063 725). Combining these sources with geographic information systems analysis, the ETT to the nearest ophthalmologist office was calculated for every resident of Kentucky, Oklahoma, and New Mexico. This study also assessed ETT to the nearest ophthalmologist for Medicare beneficiaries in those states who had received surgery from an optometrist from 2008 to 2014. Data analyses were conducted from July 2016 to July 2017. Main Outcomes and Measures: The proportion of residents of Kentucky, Oklahoma, and New Mexico who live within an ETT of 10, 30, 45, 60, or 90 minutes of the nearest ophthalmologist office. Results: The study included 4 339 367 Kentucky residents, 3 751 351 Oklahoma residents, and 2 059 179 New Mexico residents. Of these, 5 140 547 (50.6%) were female. Racial/ethnic composition included 7 154 847 people (70.5%) who were white, 640 608 (6.3%) who were black, and 1 418 246 (14.0%) who were Hispanic. The mean (SD) age was 37.8 (22.8) years. More than 75% of residents in the 3 states lived within an ETT of 30 minutes to the nearest ophthalmology office, and 94% to 99% of residents lived within an ETT of 60 minutes to the nearest ophthalmology office. Among Medicare beneficiaries who received surgery by optometrists, 58.3%, 51.1%, and 46.9% in Kentucky, Oklahoma, and New Mexico, respectively, lived within an ETT of 30 minutes from the nearest ophthalmologist office. Conclusions and Relevance: In the states where optometrists have expanded scope of practice, most residents lived within an ETT of 30 minutes of the nearest ophthalmologist office, as do half of Medicare beneficiaries who received surgical care from optometrists. These results can help inform policy makers when weighing the pros and cons of scope of practice expansion for optometrists.

Spironolactone for Secondary Central Serous Chorioretinopathy: A Challenge-Rechallenge Case.

Central serous chorioretinopathy (CSCR) is potentially sight-threatening and has been associated with corticosteroid use. CSCR secondary to steroid use can sometimes be challenging to treat, especially if continuing steroid use is medically necessary. In this case report we demonstrate the efficacy of spironolactone as an effective agent in countering CSCR secondary to steroid use. This challenge-rechallenge case may be helpful to clinicians in delineating a treatment paradigm for these patients.

Spironolactone as an Adjunctive Treatment in Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (AMD) is a potentially sight-threatening condition. The current standard-of-care treatment regimen is serial intravitreal antivascular endothelial growth factor injections. While these typically have great success, they do carry exceptional treatment burden on the patient, cost burden due to their required frequency of use, and the risk of endophthalmitis, which can be devastating. This case report explores an alternative potential option as a treatment adjunct for neovascular AMD (nAMD), and identifies some of the overlap between nAMD and central serous chorioretionpathy. Future research is needed to better understand the role of mineralocorticoid receptor antagonist treatment in this disease spectrum.

Mineralocorticoid Antagonists as Adjuncts in Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The purpose of this project was to evaluate the role of MR antagonists as an adjunct in patients with neovascular age-related macular degeneration (AMD) who have chronic subretinal fluid. METHODS: Inclusion criteria were patients with a diagnosis of neovascular AMD, who had completed at least six anti-VEGF injections, and had persistent subretinal fluid (SRF) on optical coherence tomography (OCT). Treatment with oral eplerenone was initiated and dose titrated according to protocol. RESULTS: 23 patients were included in the study (mean age = 54.6, 52.2% female, 47.8% male). 13 of the 23 patients had predominantly chronic subretinal fluid without large PEDs. In this subgroup, mean initial central macular thickness (CMT) prior to starting oral eplerenone was 305.3 µm, and mean injection interval was 40.25 days. Mean final CMT after at least 3 months of adjunctive eplerenone treatment was 240.6 µm and mean injection interval with adjunctive treatment was 54.61 days. Mean extension of the injection interval after commencing oral eplerenone was 14.36 days. CONCLUSIONS: These findings suggest oral MR antagonists may have a role as an adjunctive treatment in neovascular AMD, and may be particularly useful in dehydration of the subretinal space in the setting of chronic subretinal fluid. Further research is needed in randomized controlled trials to elucidate the precise role of oral MR antagonists in neovascular AMD.

Intravitreal Daptomycin for Recalcitrant Postoperative Endophthalmitis.

PURPOSE: To report the first case to our knowledge of intravitreal daptomycin used to successfully treat culture-negative vancomycin resistant to exogenous endophthalmitis. METHODS: Case report with preoperative, intraoperative, and postoperative findings. RESULTS: A 63-year-old Caucasian male underwent routine pars plana vitrectomy with epiretinal membrane peeling. He developed acute postoperative endophthalmitis, and underwent vitreous tap and injection of intravitreal vancomycin/ceftazidime/dexamethasone. Gram stain showed Gram-positive cocci, but cultures were negative. His infection subsequently proved very recalcitrant and his treatment course involved pars plana vitrectomy with anterior chamber washout and repeat injection of antibiotics, followed by repeat intravitreal vancomycin and ceftazidime. Ultimately, a second vitrectomy with intravitreal daptomycin controlled his intraocular infection. On each occasion, cultures were negative. CONCLUSION: This case suggests that vancomycin resistance should be considered in culture-negative postoperative endophthalmitis, and intravitreal daptomycin should be considered as an important treatment alternative. Although vancomycin resistance is fairly rare in endophthalmitis, acknowledgment of its increasing occurrence rate is critical for optimal management.

Mineralocorticoid Antagonists in the Treatment of Central Serous Chorioretinopathy: A Comparative Analysis.

BACKGROUND AND OBJECTIVE: Overaction of mineralocorticoid receptor (MR) pathways has been implicated in the pathophysiology of central serous chorioretinopathy (CSCR). The purpose of this study was to evaluate MR antagonists in the treatment of CSCR. STUDY DESIGN AND METHODS: A retrospective chart review was conducted of all CSCR patients at one center treated with spironolactone or eplerenone (50 mg p.o. b.i.d.) or observation. Patients were followed at monthly intervals with examination and optical coherence tomography. RESULTS: 32 patients (12 eplerenone, 12 spironolactone, 8 observation) were enrolled in the study. Both MR antagonists demonstrated statistically significant visual acuity improvement and subretinal fluid reduction at 1, 2, and 3 months compared to baseline (p < 0.05). 58.3% of patients had complete resolution of subretinal fluid at 2 months on MR antagonists, compared to 12.5% under observation (p < 0.05). Photodynamic therapy was used to treat refractory subretinal fluid past 6 months in 1/24 (4.2%) on MR antagonists and 2/8 (25%) patients under observation. There was no difference in efficacy between eplerenone and spironolactone. Spironolactone exhibited increased side effects (8/12, 75%) compared to eplerenone (3/12, 25%; p < 0.05). CONCLUSIONS: This data supports the use of MR antagonists in CSCR and suggests an accelerated improvement compared to observation. Prospective randomized trials are needed to better elucidate the precise role of MR antagonists in the management of CSCR.

EVALUATION OF MULTIPLE DEXAMETHASONE INTRAVITREAL IMPLANTS IN PATIENTS WITH MACULAR EDEMA ASSOCIATED WITH RETINAL VEIN OCCLUSION.

BACKGROUND: Limited data have evaluated multiple injections of the dexamethasone 700 µg implant (DEX) (Ozurdex; Allergan, Inc.) for cystoid macular edema (CME) secondary to retinal vein occlusion (RVO) over an extended regimen. METHODS: This retrospective study evaluated patients treated with DEX for CME associated with RVO. Each patient had ophthalmologic evaluation, optical coherence tomography (OCT), and 4 weeks to 6 weeks follow-up intervals. Retreatment criterion was fluid on OCT. Outcome measures included best-corrected visual acuity, intraocular pressure (IOP), central macular thickness on OCT, fluid resolution on OCT, and required treatment for elevated IOP and cataract. RESULTS: Thirty-one patients had 82 DEX injections, with 19 patients having ≥2, 12 having ≥3, 10 having ≥4, 6 having ≥5, and 4 having ≥6 DEX injections. All patients were followed at least 12 weeks and had a mean follow-up period of 344.94 days. Fourteen patients (45%) developed ocular hypertension (≥22 mmHg), and 40% of phakic patients required cataract surgery. Mean interval of OCT fluid resolution was 52 days (range, 28-245; SD, ±8), and mean retreatment interval was 119 days (range, 42-309; SD, ±9). No patients required glaucoma surgery or developed endophthalmitis. CONCLUSION: This study suggests that repeated, as needed, DEX injections for CME associated with RVO may be performed. Patients should be monitored and treated for ocular hypertension and cataract progression.

Vascular smooth muscle LRP6 limits arteriosclerotic calcification in diabetic LDLR-/- mice by restraining noncanonical Wnt signals.

RATIONALE: Wnt signaling regulates key aspects of diabetic vascular disease. OBJECTIVE: We generated SM22-Cre;LRP6(fl/fl);LDLR(-/-) mice to determine contributions of Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6) in the vascular smooth muscle lineage of male low-density lipoprotein receptor-null mice, a background susceptible to diet (high-fat diet)-induced diabetic arteriosclerosis. METHODS AND RESULTS: As compared with LRP6(fl/fl);LDLR(-/-) controls, SM22-Cre;LRP6(fl/fl);LDLR(-/-) (LRP6-VKO) siblings exhibited increased aortic calcification on high-fat diet without changes in fasting glucose, lipids, or body composition. Pulse wave velocity (index of arterial stiffness) was also increased. Vascular calcification paralleled enhanced aortic osteochondrogenic programs and circulating osteopontin (OPN), a matricellular regulator of arteriosclerosis. Survey of ligands and Frizzled (Fzd) receptor profiles in LRP6-VKO revealed upregulation of canonical and noncanonical Wnts alongside Fzd10. Fzd10 stimulated noncanonical signaling and OPN promoter activity via an upstream stimulatory factor (USF)-activated cognate inhibited by LRP6. RNA interference revealed that USF1 but not USF2 supports OPN expression in LRP6-VKO vascular smooth muscle lineage, and immunoprecipitation confirmed increased USF1 association with OPN chromatin. ML141, an antagonist of cdc42/Rac1 noncanonical signaling, inhibited USF1 activation, osteochondrogenic programs, alkaline phosphatase, and vascular smooth muscle lineage calcification. Mass spectrometry identified LRP6 binding to protein arginine methyltransferase (PRMT)-1, and nuclear asymmetrical dimethylarginine modification was increased with LRP6-VKO. RNA interference demonstrated that PRMT1 inhibits OPN and TNAP, whereas PRMT4 supports expression. USF1 complexes containing the histone H3 asymmetrically dimethylated on Arg-17 signature of PRMT4 are increased with LRP6-VKO. Jmjd6, a demethylase downregulated with LRP6 deficiency, inhibits OPN and TNAP expression, USF1: histone H3 asymmetrically dimethylated on Arg-17 complex formation, and transactivation. CONCLUSIONS: LRP6 restrains vascular smooth muscle lineage noncanonical signals that promote osteochondrogenic differentiation, mediated in part via USF1- and arginine methylation-dependent relays.