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To describe a patient with a choroidal osteoma treated with photodynamic therapy to prevent tumor growth in whom choroidal neovascularization (CNV) developed after being treated with photodynamic therapy.Case report.A 5-year-old Hispanic woman presented with an asymptomatic choroidal osteoma, temporal to the macula of her right eye. According to the patient's mother, her medical, surgical, and family history was unremarkable. At examination, best-corrected visual acuity was 20/30 in both eyes. After 11 months of follow-up, signs of tumor growth toward the fovea without any signs of CNV was noted. Photodynamic therapy was performed to prevent invasion of the foveola. Two months thereafter, the patient developed CNV in the macula region in the right eye, decreasing visual acuity to 20/200. The patient was treated with four total intravitreal injections of 1.25 mg of bevacizumab over 24 weeks, which resulted in inactivation of the CNV and improved visual acuity to 20/20. Choroidal neovascularization had been never reported in her past history and her follow-up visits over 7 years. In addition, no evidence of recurrent neovascular activity or tumor growth was reported.Choroidal osteoma is a benign tumor that can result in vision-threatening complications, caused by tumor growth and tumor decalcification. Photodynamic therapy is an effective modality in inducing choroidal osteoma decalcification and stabilization; however, CNV due to reperfusion following photodynamic therapy can be seen in the retina.

PURPOSE: Intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) are the current standard of care for patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). There is a growing subset of patients that does not respond to anti-VEGF monotherapy treatment. Some patients, however, do respond to a combination therapy of corticosteroids and anti-VEGF. This treatment requires monthly/bimonthly injections of anti-VEGF and semi-annual injections of corticosteroid. A drug delivery system (DDS) that simultaneously releases multiple drugs could benefit these patients by reducing the number of injections. The purpose of this study was to characterize the simultaneous release of aflibercept and dexamethasone from a biodegradable microparticle- and nanoparticle-hydrogel DDS. METHODS: Dexamethasone-loaded nanoparticles and aflibercept-loaded microparticles were created using modified single- and double-emulsion techniques, respectively. Then, microparticles and nanoparticles were embedded into a thermoresponsive, biodegradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate (PEG-PLLA-DA)-N-isopropylacrylamide (NIPAAm) hydrogel DDS. Drug release studies and characterization of DDS were conducted with varying doses of microparticles and nanoparticles. RESULTS: The combination aflibercept-loaded microparticle- and dexamethasone-loaded nanoparticle- hydrogel (Combo-DDS) achieved a total release time of 224 days. Small decreases were seen in swelling ratio and equilibrium water content for Combo-DDS compared to monotherapy aflibercept-loaded microparticle-hydrogel DDS (AFL-DDS) and monotherapy dexamethasone-loaded nanoparticle-hydrogel DDS (DEX-DDS). Bioactivity of aflibercept was maintained in Combo-DDS compared to AFL-DDS. CONCLUSIONS: The Combo-DDS was able to extend and control the release of both aflibercept and dexamethasone simultaneously from a single DDS. This may eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for wet AMD patients.

PURPOSE To describe four cases of varix of the vortex vein ampulla imaged with dynamic echography. METHODS Observational case series of four patients with varix of the vortex vein ampulla diagnosed with ocular examination maneuvers such as digital pressure or Valsalva. Dynamic echography was used to confirm the diagnosis. RESULTS Dynamic echography can quickly and noninvasively show the varix of the vortex vein ampulla disappear with external pressure, or engorge with a Valsalva maneuver or altered gaze directions. CONCLUSION Dynamic echography is very helpful in the establishment of the diagnosis of varix of the vortex vein ampulla and differentiating this benign condition from other retinal or choroidal abnormalities.

Background/purpose To describe the use of topical mitomycin-C in sclerostomy revision for recalcitrant idiopathic uveal effusion syndrome. Methods A 50-year-old healthy man presented with painless, gradual vision loss in the right eye. He underwent multimodal retinal imaging with wide-field fundus photography, spectral domain optical coherence tomography, and B-scan and A-scan ultrasonography. He was found to have idiopathic (non-nanophthalmic) uveal effusion syndrome with choroidal and serous retinal detachments in the right eye and a peripheral choroidal detachment in the left eye. Central vision became threatened in the right eye. Medical treatment with oral corticosteroids and surgical treatment with choroidal drainage through sclerostomies and sclerostomy revision were administered. Results Initial treatment with systemic corticosteroids was ineffective. Subsequent choroidal drainage through sclerostomies only partially resolved the effusion. Later sclerostomy revision with application of topical mitomycin-C led to complete resolution with anatomical stability maintained after at least 42 months of follow-up. Conclusion Successful use of topical mitomycin-C in sclerostomy revision has not previously been reported in idiopathic (non-nanophthalmic) uveal effusion syndrome. We propose that topical mitomycin-C may be considered as a potential therapeutic adjunct in the treatment of refractory idiopathic uveal effusion syndrome before further sclerostomy procedures are attempted in additional quadrants of the eye.

Recent advances in pharmacological agents have led to successful treatment of a variety of retinal diseases such as neovascular age-related macular degeneration (AMD), diabetic macular oedema (DMO), and retinal vascular occlusions (RVO). These treatments often require repeated drug injections for an extended period of time. To reduce these repeated treatment burdens, minimally invasive drug delivery systems are needed. An ideal therapy should maintain effective levels of drug for the intended duration of treatment following a single application, recognising that a significant number of months of therapy may be required. There are numerous approaches under investigation to improve treatment options. This review will highlight the advantages and limitations of selected drug delivery systems of novel biomaterial implants and depots. The main emphasis will be placed on less invasive, longer acting, sustained release formulations for the treatment of retinal disorders.摘要: 近年来, 药理学方面的进步改善了多种视网膜疾病的预后, 例如新生血管性年龄相关性黄斑变性 (AMD), 糖尿病性黄斑水肿 (DMO) 和视网膜血管阻塞 (RVO)。此类疾病的治疗通常需要长期反复注射给药, 为了减少重复性治疗的负担, 尽可能使用无创的药物传输系统。考虑到可能需要数月的治疗周期, 理想的治疗方式是在单次给药后较长时间内能保持有效的药物浓度。目前多种药物正在研发之中以改善药物治疗方案。本篇综述概括了几种特定的新型生物材料植入物和缓释库给药途径的优势和局限性。重点介绍了治疗视网膜疾病的侵入性小, 作用时间长, 持续性释放的几种制剂。.

An intact blood-retinal barrier is critical to maintaining the function of the retina. Many diseases of the eye have been directly associated with impairment in vascular permeability, and methods to measure vascular permeability could offer a window into early detection of disease; however, there exist no direct measures of vascular permeability that have be translated to the clinic. This work details a complete clinical workflow to quantify vascular permeability and volumetric blood flow from fluorescein videoangiography data, with validation through realistic simulations. For optimizing the protocol, this study carried on frame rate of fluorescein videoangiography to generate a high-resolution image while minimizing the error.

Purpose To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift’s electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma. Design Multicenter, retrospective case series and literature review. Participants Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases). Methods The clinical data of 17 eyes were pooled. Spearman’s correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes. Main Outcome Measures Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]). Results In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up. Conclusions Thomas A. Swift’s electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.

Upon completion of this activity, participants will be able to: In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Springer Nature. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at www.medscape.org/journal/eye; (4) view/print certificate. 1.0 Release date: Expiration date: November 23rd 2021 Post-test link: https://medscape.org/eye/posttest938103 S.S. has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Allergan, Inc.; Apellis; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Heidelberg Pharma GmbH; Novartis; Oculis; Optos; Oxurion; Roche. Served as a speaker or a member of a speakers bureau for: Allergan, Inc.; Bayer AG; Novartis Pharmaceuticals Corporation; Optos. Received grants for clinical research from: Allergan, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Optos. T.E.d.C. and W.F.M. have disclosed no relevant financial relationships. Charles P. Vega, MD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: GlaxoSmithKline. To determine if commercial OCTA measurements can provide quantitative biomarkers for detection of radiation retinopathy (RR) s/p I-125 plaque brachytherapy in patients with uveal melanoma. Retrospective review of 6 × 6 mm OCTA images of nonirradiated fellow eyes (group 1, 28 eyes), eyes without RR (group 2, 22 eyes), eyes with RR (group 3, 13 eyes). We used automated AngioVue AngioAnalytics OCTA software determinations of FAZ size, perimeter size, and 27 capillary density measurements (nine regions of each segmentation: full-thickness retina, superficial plexus, deep plexus). Average time since irradiation was 1.9 years in group 2, and 3.7 years in group 3. FAZ size was 1.2 mm in group 3 compared with 0.2 mm in group 1 and 0.3 mm in group 2 (both p

Purpose To evaluate the in vivo treatment efficacy and biocompatibility of a biodegradable aflibercept-loaded microsphere-hydrogel drug delivery system (DDS) in a laser-induced choroidal neovascularization (CNV) rat model. Methods Two weeks after CNV induction, animals were randomly assigned into four experimental groups: (1) no treatment, (2) single intravitreal (IVT) injection of blank DDS, (3) bimonthly bolus IVT aflibercept injections, and (4) single IVT injection of aflibercept-DDS. CNV lesion sizes were monitored longitudinally using fluorescence angiography and multi-Otsu thresholding for 6 months. For safety and biocompatibility assessment, an additional three non-CNV animals received a blank DDS injection. Electroretinogram, intraocular pressure, and clinical ophthalmoscopic examinations were performed. Results The average lesion areas at week 0 (treatment intervention) were (1) 8693 ± 628 µm2 for no treatment, (2) 8261 ± 709 µm2 for blank DDS, (3) 10,368 ± 885 µm2 for bolus, and (4) 10,306 ± 1212 µm2 for aflibercept-DDS. For the nontreated groups, CNV lesion size increased by week 2 and remained increased throughout the study. The treated groups exhibited CNV size reduction after week 2 and remained for 6 months. At week 22, the average percent changes in CNV lesion area were +38.87% ± 7.08%, +34.19% ± 9.93%, -25.95% ± 3.51%, and -32.69% ± 5.40% for the above corresponding groups. No signs of chronic inflammation and other ocular abnormalities were found. Conclusions The aflibercept-DDS was effective in treating CNV lesions for 6 months and is safe, well tolerated, and biocompatible. Translational relevance The proposed DDS is a promising system to reduce IVT injection frequency for anti-vascular endothelial growth factor treatment.

The proposed doses of chloroquine (CQ) and hydroxychloroquine (HCQ) for treatment of COVID-19 (1000 mg/day for 10 days, CQ; 800 mg first day then 400 mg/day for 5 days, HCQ) in many guidelines worldwide, are considerably higher than the maximum recommended daily safe doses of both agents (≤2.3 mg/kg/day, CQ; ≤5.0 mg/kg/day, HCQ) for development of retinal toxicity. Irreversible retinal damage can occur if the exposure to the safe doses is >5 years. It is not known whether exposure to high doses over a short period of time can also cause the damage. We recommend that before prescribing CQ or HCQ, history of ocular disease should be obtained to avoid the prescription if appropriate. If either agent is to be used, routine baseline ocular examination is not absolutely necessary. Patients who do not have ocular disease should also be informed about the potential risk of retinal toxicity. Both agents, however, have not yet been proven to be beneficial to COVID-19.

Author(s): Kim, Soohyun; Kang-Mieler, Jennifer J; Liu, Wenqiang; Wang, Zhe; Yiu, Glenn; Teixeira, Leandro BC; Mieler, William F; Thomasy, Sara M | Abstract: PurposeTo evaluate the safety and tolerability of a microsphere thermo-responsive hydrogel drug delivery system (DDS) loaded with aflibercept in a nonhuman primate model.MethodsA sterile 50 µL of aflibercept-loaded microsphere thermo-responsive hydrogel-DDS (aflibercept-DDS) was injected intravitreally into the right eye of 10 healthy rhesus macaques. A complete ophthalmic examination, intraocular pressure (IOP) measurement, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and electroretinogram were performed monthly for 6 months. One macaque was euthanized monthly, and the enucleated eyes were submitted for measurement of bioactive aflibercept concentrations. Four eyes were submitted for histopathology.ResultsInjected aflibercept-DDS was visualized in the vitreous until 6 months postinjection. No abnormalities were observed in the anterior segment, and IOP remained within normal range during the study period. A small number of cells were observed in the vitreous of some macaques, but otherwise the remainder of the posterior segment examination was normal. No significant changes in retinal architecture or function as assessed by SD-OCT and histology or full-field electroretinography, respectively, were observed. A mild, focal foreign body reaction around the injectate was observed with histology at 6 months postinjection. A mean of 2.1 ng/µL of aflibercept was measured in the vitreous.ConclusionsIntravitreally injected aflibercept-DDS achieved controlled, sustained release of aflibercept with no adverse effects for up to 6 months in the eyes of healthy rhesus macaques.Translational relevanceAflibercept-DDS may be a more effective method to deliver bioactive antivascular endothelial growth factor agents than current practice by reducing the frequency of intravitreal injections and providing controlled drug release.

Fluorescein videoangiography is often used to visualize diabetic retinopathy (DR), a degenerative disease characterized by degradation of retinal blood vessels. However, more sensitive and quantitative measures of increased vessel permeability in the asymptomatic phase of DR (non-proliferative DR) could help identify patients who would benefit from therapeutic intervention to avoid vision loss. Here, a modified “adiabatic approximation to the tissue-homogeneity model” was shown in simulations and rat experiments to estimate extraction fraction within a 20%-error for physiological ranges of vascular permeability expected in nonproliferative DR, even in low-dynamic-range (8-bit) fluorescein imaging systems that are standard in many institutes.

Demonstrate in vivo that controlled and extended release of a low dose of anti-vascular endothelial growth factor (anti-VEGF) from a microsphere-hydrogel drug delivery system (DDS) has a therapeutic effect in a laser-induced rat model of choroidal neovascularization (CNV).Anti-VEGF (ranibizumab or aflibercept) was loaded into poly(lactic-co-glycolic acid) microspheres that were then suspended within an injectable poly(N-isopropylacrylamide)-based thermo-responsive hydrogel DDS.The DDS was shown previously to release bioactive anti-VEGF for ~200 days. CNV was induced using an Ar-green laser. The four experimental groups were as follows: (i) non-treated, (ii) drug-free DDS, (iii) anti-VEGF-loaded DDS, and (iv) bolus injection of anti-VEGF. CNV lesion areas were measured based on fluorescein angiograms and quantified using a multi-Otsu thresholding technique. Intraocular pressure (IOP) and dark-adapted electroretinogram (ERG) were also obtained pre- and post-treatment (1, 2, 4, 8, and 12 weeks).The anti-VEGF-loaded DDS group had significantly smaller (60%) CNV lesion areas than non-treated animals throughout the study. A small transient increase in IOP was seen immediately after injection; however, all IOP measurements at all time points were within the normal range. There were no significant changes in ERG maximal response compared to pre-treatment measurements for the drug-loaded DDS, which suggests no adverse effects on retinal cellular function.The current study demonstrates that the DDS can effectively decrease laser-induced CNV lesions in a murine model. Controlled and extended release from our DDS achieved greater treatment efficacy using an order of magnitude less drug than what is required with bolus administration. This suggests that our DDS may provide a significant advantage in the treatment of posterior segment eye diseases.

Purpose: To report indications and outcomes of combined pars plana vitrectomy and penetrating keratoplasty (PPV-PKP). Methods: A review of all patients who underwent PPV-PKP at the Illinois Eye and Ear Infirmary from January 1, 2001 to May 31, 2013, was performed. Ninety eyes of 90 patients were identified. Survival analysis was utilized to assess differences in retinal detachment (RD) and corneal graft failure rates among groups based on clinical and surgical variables. Results: Seventy-nine eyes met the inclusion criteria. Most common indications for vitrectomy and corneal transplantation were RD (65%) and corneal decompensation (43%), respectively. The preoperative and final visual acuity (VA) logarithm of the minimum angle of resolution values were 2.7 (0.31) and 2.5 (0.67) (hand motions; mean [SD]; P = .02); 15% of eyes were ≥20/400 and 15% gained ≥2 lines of vision following surgery. Corneal graft failure occurred in 51% (40 eyes), recurrent RD in 28% (22 eyes), and hypotony in 25% (20 eyes). Silicone oil endotamponade was associated with postoperative RD ( P = .045), and previous ocular trauma was associated with postoperative corneal graft failure ( P = .023). Conclusion: Combined PPV-PKP surgery was likely to achieve stabilization of VA, with a minority of eyes achieving modest gains in VA.

The need for sustained ocular drug delivery systems grows with the increasing number of people with visual impairments. Drug delivery to the posterior segment poses unique challenges that a variety of systems have been developed to overcome. Currently, small-molecule drugs and protein therapeutics are mainly administered as topical solutions and intravitreal injections, respectively. Small-molecule drugs have a short half-life and diffuse easily throughout the eye, making it challenging to deliver a localized, and maintained, therapeutic dose. The main challenge of delivery protein therapeutics is maintaining a sustained therapeutic level of protein during manufacture and release since most protein therapeutics depend on their complex structural integrity to be effective. Due to these limitations, repeated doses of small-molecule drugs and protein therapeutics are given to maintain a therapeutic range. Thus, developing new drug delivery systems (DDSs) that have a controlled, extended, and localized release of drug and maintain drug stability would reduce the frequency of administration. This chapter discusses new DDSs for small-molecule and macromolecular biological drugs, particularly protein therapeutics, in the form of ocular implants, ocular inserts, microneedles, cell-based systems, injectable nano/microparticles, injectable hydrogels, and composite systems. Many of these advances in drug delivery will help to play a role in improving anatomic and visual outcomes for various forms of macular surgery.

The use of robotic-assisted surgery has been successfully implemented in many surgical fields including, but not limited to, general surgery, cardiology, urology, and gynecology. The introduction of this technology has been increasingly accepted due to the surgical precision and dexterity required for certain procedures that may be at or beyond the limits of human capabilities. In ophthalmology, robotic-assisted surgery has not yet been widely adopted, though many robotic prototypes show great promise to improve surgical techniques, and ultimately patient outcomes. In this chapter, we review the advantages, surgical approaches, indications, limitations, and future developments of robotic-assisted surgery as it relates to the vitreoretinal surgeon.

Purpose: This case report discusses the management of a patient with a superior chorioretinal coloboma-associated retinal detachment (RD), including surgical management, along with a review of the literature. Methods: A case report is presented. Results: A 58-year-old man presented with a chronic RD of the right eye that was symptomatic for approximately 1 year prior to presentation. On examination, he was found to have a macula-off RD associated with superior chorioretinal coloboma. He underwent 23-gauge pars plana vitrectomy with membrane peel, endolaser, and perfluoropropane (14%) gas tamponade. Three months after his surgery, his best-corrected visual acuity in his right eye was 20/250 distance and 20/80 near, and his retina remained attached. Conclusions: This case report describes surgical management of a superior chorioretinal coloboma-associated RD.

Purpose: This article reports the presentation, management, and outcomes in patients suffering perforating ocular injuries. Methods: A retrospective review was conducted at a single ophthalmology Level 1 trauma center. Patients with evidence of traumatic ocular perforation, with surgical intervention attended by a single vitreoretinal surgeon (W.F.M.), were reviewed between 2009 and 2017. Results: Six eyes from 6 patients with perforating ocular injuries were studied. All patients were male, between ages 11 and 56 years. Perforation was the result of gunshots (3), other accidental injury (2), or surgical complication (1). Varying degrees of retinal detachments were seen in all 6 patients. Pars plana vitrectomy, with endolaser around posterior entry or exit wounds, was performed on average 21.7 ± 8.9 days from the time of injury (range, 0-58 days). In all cases with intraorbital foreign bodies, the foreign bodies were left in place. The most recent postoperative visual acuity ranged from 20/25 to counting fingers. Missile injuries tended to have poorer vision. All cases achieved full anatomic attachment at most recent follow-up. There have been no orbital complications related to retained intraorbital foreign bodies, including endophthalmitis, orbital infections, or mechanical strabismus. Conclusion: This study demonstrates successful anatomic outcomes of 6 cases of perforating ocular injuries. Visual outcomes were variable, though missile injuries demonstrated worse prognosis, whereas several nonmissile macula-involving cases achieved quite favorable results. Although traumatic perforating injuries generally have guarded visual prognoses, favorable results may be achieved in select scenarios.

Purpose: We report a case of an otherwise healthy 48-year-old woman presenting with acute vision loss after injection of a soft-tissue filler in the glabellar region with calcium hydroxylapatite microspheres (Radiesse, Merz North America, Inc) with 9 months of follow-up. Methods: Fundus photographs and spectral-domain optical coherence tomography (SD-OCT) were obtained at presentation, at 4 months of follow-up, and at 9 months of follow-up. Results: Acutely, the retina was characterized by significant pallor and thickening but evolved into diffuse retinal fibrosis and atrophy. The patient had no light perception at presentation and did not recover any visual function. Conclusions: Few case reports have described calcium hydroxylapatite filler injections leading to orbital and ocular complications. This is the first case report illustrating dense fibrotic and atrophic retinal changes on fundus photography, fluorescein angiography, and SD-OCT. While various facial fillers have been reported to have serious ocular consequences, we illustrate the acute and subsequent sequelae of an ophthalmic artery occlusion from calcium hydroxylapatite microspheres.

Background The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. Pattern of Retinopathy Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. Dose We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight. Risk of Toxicity The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year. Major Risk Factors High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen. Screening Schedule A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors. Screening Tests The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus. Toxicity Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication. Counseling Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening.

BackgroundTo demonstrate a technique for using optical coherence tomography angiography (OCTA) to simulate leakage in eyes with diabetic macular oedema and determine the sensitivity and positive predictive value of detecting leaking microvasculature on OCTA using fluorescein angiography (FA) as the comparative norm.Methods6×6 mm OCT angiograms were overlaid with the corresponding OCT thickness maps. Microvascular abnormalities on the OCT angiogram underlying areas of thickening on the OCT thickness map were assumed to be leaking. Two independent readers blindly read the OCTA overlay images then the FA images cropped to the same approximate region to delineate areas of leaking microvasculature. The results were compared to determine the sensitivity and positive predictive value of OCTA for detection of leaking vessels.Results28 eyes of 19 diabetic patients were included. Each eye demonstrated an average of seven leaking microvascular abnormalities on the OCTA images and 22 leaking abnormalities on the FA images. Sensitivity of leaking microvasculature detection by OCTA was 26.1% and positive predictive value was 68.4%. The correlation coefficient of the two readers’ detection of leaking microvasculature was 0.605 for OCTA reads compared with 0.916 for FA.ConclusionOCTA as a whole can be used to simulate leakage, but currently, sensitivity of the technique is low. Further understanding of the OCTA technology may yield novel means of detecting retinal pathology.

Background. An ophthalmology consultation service is of significant benefit to patients in the hospital and is an instructive component of a residency education program. Ophthalmology consultations in a hospital present unique challenges to those seen in an outpatient clinic, for which the consulting ophthalmologist should be prepared. The purpose of this study was to profile the emergency room and inpatient ophthalmology consultations seen at an academic institution. Methods. A prospective study of 581 patients was conducted on inpatient and emergency room ophthalmology consultations at the University of Illinois at Chicago over twelve months. Characteristics such as the consulting service, type of and reason for consultation, subspecialty staffing service, diagnosis, and suitability for in-hospital evaluation were recorded. Results. Consultations were received from either inpatient wards (59.4%) or the Emergency Department (40.6%). The most common inpatient consulting services were internal medicine (22%), followed by neurosurgery (16%) and neurology (7%). All the consultations were categorized as acute (72.3%), chronic (6.0%), or screening (21.7%). Consultations categorized as screening included papilledema (31.0%), fungemia (20.6%), syndromic evaluation (19.8%), visual field evaluation (17.5%), and miscellaneous evaluation (11.1%). We classified the ophthalmic diagnoses into 63 unique diagnoses. Amongst the ophthalmic subspecialties, neuro-ophthalmologic diagnoses were the most common (32.0%), followed by retina (20.1%) and cornea (19.4%). Neuro-ophthalmology had the highest proportion of screening consultations (36.6%), while glaucoma had the least overall number of consultations (10.1%), and the least proportion of screening consultations (3.6%). A significant proportion of nonacute consultations (19.0%) was deemed to be more suitable for outpatient evaluation. Discussion. Consultation databases can be useful in preparing trainees for in-hospital clinical care. A wide range of ocular pathologies may present to the ophthalmology consultant, from acute trauma to screening for systemic syndromes. Some consultations may be more suitable for outpatient evaluation which may help optimize patient care.

PURPOSE: Current standard of care for neovascular eye diseases require repeated intravitreal bolus injections of anti-vascular endothelial growth factors (anti-VEGFs). The purpose of this study was to validate a degradable microsphere-thermoresponsive hydrogel drug delivery system (DDS) capable of releasing bioactive aflibercept in a controlled and extended manner for 6 months. MATERIALS AND METHODS: The DDS was fabricated by suspending aflibercept-loaded poly(lactic-coglycolic acid) microspheres within a biodegradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate/N-isopropylacrylamide (PEG-PLLA-DA/NIPAAm) thermoresponsive hydrogel. Encapsulation efficiency of DDSs and in vitro release profiles were characterized by iodine-125 radiolabeled aflibercept. The degradation of hydrogel was determined by dry weight changes. The cytotoxicity from degraded DDS byproducts was investigated by quantifying cell viability using LIVE/DEAD® assay. In addition, dot blot and enzyme-linked immunosorbent assay were used to determine the bioactivity of released drug. Finally, morphology of microspheres and hydrogel were investigated by cryo-scanning electron microscopy before and after thermal transformation. RESULTS: The microsphere-hydrogel DDS was capable of releasing bioactive aflibercept in a controlled and extended manner for 6 months. The amount and rate of aflibercept release can be controlled by both the cross-linker concentration and microspheres load amount. The initial burst (release within 24 h) was from 37.35 ± 4.92 to 74.56 ± 6.16 μg (2 and 3 mM hydrogel, each loaded with 10 and 20 mg/ml of microspheres, respectively), followed by controlled drug release of 0.07–0.15 μg/day. Higher PEG-PLLA-DA concentration (3 mM) degraded faster than the lower concentration (2 mM). No significant cytotoxicity from degraded DDS byproducts was found for all investigated time points. Bioactivity of released drug was maintained at therapeutic level over entire release period. CONCLUSIONS: The microsphere-hydrogel DDS is safe and can deliver bioactive aflibercept in a controlled manner. This may provide a significant advantage over current bolus injection therapies in the treatment of ocular neovascularization.

Purpose To characterize a biodegradable microsphere-hydrogel drug delivery system (DDS) for controlled and extended release of ranibizumab. Methods The degradable microsphere-hydrogel DDSs were fabricated by suspending ranibizumab-loaded or blank poly(lactic-co-glycolic acid) microspheres within a poly(ethylene glycol)-co-(L-lactic-acid) diacrylate/N-isopropylacrylamide (PEG-PLLA-DA/NIPAAm) hydrogel. The thermal responsive behavior of various DDS formulations was characterized in terms of volume phase transition temperature (VPTT) and swelling ratios changes from 22°C to 42°C. The mechanical properties were characterized using rheological methods. Degradability of hydrogels were also examined via wet weight loss. Finally, Iodine-125 was used to radiolabel ranibizumab for characterization of encapsulation efficiency and in vitro release. Results All DDS formulations investigated were injectable through a 28-gauge needle at room temperature. The VPTT increased with increase of cross-linker concentration. The swelling ratios decreased as temperature increased and were not influenced by presence of microspheres. Rheology data confirmed that increase of cross-linker concentration and microsphere loading made DDS stiffer. Increase of degradable cross-linker concentration facilitated hydrogel in vitro degradation. Controlled release of ranibizumab were achieved for investigated DDS formulations for 6 months; and increased degradable cross-linker concentration produced faster and more complete release. Conclusions The biodegradable DDSs are suitable for sustained release of ranibizumab. Considering ease of injection, degradability and release of ranibizumab, DDS with 3 mM cross-linker concentration and less than 20 mg/mL microsphere loadings is more favorable for future application. Translational relevance The investigated DDS is promising for controlled and extended release of anti-VEGF therapeutics to achieve better treatment regimen in ocular neovascularizations.

To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift's electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma.Multicenter, retrospective case series and literature review.Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases).The clinical data of 17 eyes were pooled. Spearman's correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes.Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]).In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up.Thomas A. Swift's electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.

Several medications are associated with retinal vascular toxicity. These include intraocular aminoglycosides, oral contraceptives, interferon alpha, several other agents, and talc, which occurs as a vehicle in some oral medications that may be abused intravenously. As a group, these entities represent a small but clinically relevant category of retinal toxicity from medications. Some of the manifestations (e.g., retinal vascular occlusion) are nonspecific, but others are more specific, including clinically visible talc emboli in retinal vessels. Toxicity may be asymptomatic or may cause irreversible visual loss. By maintaining a high index of suspicion, the correct diagnosis can usually be made.

PurposeTo report bilateral hemorrhagic retinopathy in an adult female subject after lumbar spinal surgery and seizure.Case ReportA 38-year-old woman presented with bilateral blurry vision and spots in the visual field. The patient had lumbar spondylosis surgery that was complicated by a dura

Purpose To report outer retinal disruption and uveal effusion after gemcitabine and docetaxel combination therapy. Case report A 78-year-old woman presented with blurry vision after two cycles of gemcitabine and docetaxel combination chemotherapy for stage IV sarcoma. At presentation, visual acuity was finger counting and 20/25 in the right and left eyes, respectively. Slit-lamp examination and B-scan ultrasonography revealed severe uveal effusion in the right eye and choroidal folds in the left eye. Spectral domain optical coherence tomography showed disruption of photoreceptor inner segment ellipsoid band in the right eye. The patient was monitored weekly with ophthalmic examination and B-scan ultrasonography, while continuing with gemcitabine monotherapy. At 8 weeks follow-up, uveal effusion improved considerably and visual acuity was 20/40 and 20/20 in the right and left eyes, respectively. Conclusions Uveal effusion and outer retinal disruption were reported after gemcitabine and docetaxel chemotherapy. Early detection and close ophthalmic monitoring may allow concurrent cancer treatment and prevention of possible chemotherapy-induced ocular side effects.

Closed-globe blunt ocular trauma is a major medical, epidemiologic, and economic concern due to the high risk of severe vision loss. Types of closed-globe trauma can be divided into two categories: direct and indirect. Direct trauma includes traumatic retinal tear, detachment, and dialysis, traumatic macular hole, commotio retinae, contusion of the retinal pigment epithelium, choroidal rupture, chorioretinitis sclopetaria, and optic nerve avulsion. Indirect ocular trauma includes Valsalva retinopathy, solar and laser-induced retinopathy, Terson syndrome, Purtscher retinopathy, shaken baby syndrome, fat embolism syndrome, and whiplash retinopathy. Awareness of these conditions may help increase early detection and prevent reversible vision loss.