COLORADO AGE-RELATED MACULAR DEGENERATION REGISTRY: Design and Clinical Risk Factors of the Cohort.

PURPOSE: To study new and existing risk factors related to age-related macular degeneration (AMD) phenotypes in a Colorado cohort. METHODS: Age-related macular degeneration was categorized into early, intermediate, or advanced forms. Controls (n = 180) were patients with cataract and no AMD. Demographic and clinical data were gathered by patient interview and verified by chart review. Image data were reviewed by vitreoretinal specialists. Statistical analysis included univariable and multivariate logistic regression analysis (P < 0.05). RESULTS: Among the 456 patients with AMD, 157 (34.4%), 80 (17.6%), and 219 (48.0%) had the early/intermediate, geographic atrophy, and neovascular forms of the disease, respectively. Adjusted for age, African-American race was associated with a reduced risk of early/intermediate (adjusted odds ratio [AOR] = 0.08, confidence interval [CI] = 0.01-0.67) and neovascular AMD (AOR = 0.15, CI = 0.03-0.72). A family history of AMD was a risk factor for early/intermediate (AOR = 4.08, CI = 2.30-7.25), geographic atrophy (AOR = 8.62, CI = 3.77-19.7), and neovascular AMD (AOR = 3.76, CI = 2.16-6.56). A history of asthma was related to the early/intermediate form of AMD (AOR = 2.34, CI = 1.22-4.46). CONCLUSION: Studying AMD in specific populations may reveal novel risk factors such as our finding of a relationship between asthma history and AMD.

The DISCOVER Study 3-Year Results: Feasibility and Usefulness of Microscope-Integrated Intraoperative OCT during Ophthalmic Surgery.

PURPOSE: To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. DESIGN: Prospective, consecutive case series. PARTICIPANTS: Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. METHODS: The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. MAIN OUTCOME MEASURES: Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. RESULTS: Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%-98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%-49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%-33.0%). CONCLUSIONS: The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.

Trends in treatment strategies for suspected bacterial endophthalmitis.

PURPOSE: To describe how vitreoretinal specialists have incorporated the Endophthalmitis Vitrectomy Study (EVS) findings into current practice, to highlight divergences from the EVS recommendations, and address the role of microbial culture in guiding additional treatments. METHODS: This is a cross-sectional survey of vitreoretinal specialists regarding indications used for performing a pars plana vitrectomy (PPV), selection of antibiotics for treatment, utilization of cultures, and treatment strategies for treatment-refractory patients with bacterial endophthalmitis. RESULTS: Of 681 physicians contacted, 149 (21.9%) responded. For patients with visual acuity of light perception or less, 75% of respondents utilized PPV. Intravitreal vancomycin and ceftazidime were used by 100% and 96% of participants respectively. Vitreal cultures were obtained more than 50% of the time by 86.5% of participants, and were used to influence retreatment less than 50% of the time by 77.8% of respondents. For patients with worsening clinical signs 48 hours after initial treatment, 69.8% of participants performed PPV with intravitreal antibiotics. CONCLUSIONS: Although most respondents followed the EVS guidelines, a minority deviated, and the majority generalized their strategy to other forms of endophthalmitis. There is significant variation in retreatment strategies, and while cultures are frequently obtained to help guide these treatments, they are utilized infrequently.

Checkpoint inhibitor-induced uveitis: a case series.

PURPOSE: Checkpoint inhibitors are now a common treatment modality for metastatic cancer. In this manuscript, we describe the clinical features and management of autoimmune non-infectious uveitis induced by this class of drugs. METHODS: Seven patients undergoing checkpoint inhibitor treatment for metastatic cancer from uveitis practices at three tertiary referral centers. RESULTS: All seven patients developed various severities of ocular inflammatory disease while taking checkpoint inhibitors for metastatic disease. CONCLUSIONS: Checkpoint inhibitors may induce autoimmune uveitis. Ocular complaints should prompt an early evaluation by an ophthalmologist.

Herpes zoster keratitis development after acute retinal necrosis.

PURPOSE: To report a case of herpes zoster keratitis in a patient undergoing treatment for herpetic acute retinal necrosis. METHODS: Case report. RESULTS: A 71 year old male presented with acute retinal necrosis of the left eye due to herpes zoster and was treated with intravitreal foscarnet and oral valcyclovir. He developed a retinal detachment and underwent surgical repair. After four weeks, he developed an ipsilateral herpetic zoster keratitis demonstrated by Rose-Bengal staining that was responsive to topical ganciclovir gel. CONCLUSIONS: This case report describes the unusual development of herpes zoster keratitis after the development of unilateral acute retinal necrosis (ARN) in a patient on antiviral treatment.

Current phase 1/2 research for neovascular age-related macular degeneration.

PURPOSE OF REVIEW: The purpose of this review is to provide an update of phase 1 and 2 clinical trials in neovascular age-related macular degeneration that are either currently underway or recently completed by the end of 2014. RECENT FINDINGS: Three gene therapy options are currently in early clinical trials, administered via intravitreal (AAV2-sFLT01) or subretinal (AVA-101 and RetinoStat) injection to express angiogenesis inhibitors. Several eye drops are being developed for topical administration for various angiogenic inhibitors, including regorafenib, squalamine lactate, and PAN-90806. Early development of systemic administration options may be intravenous (iSONEP) or oral (X-82). Initial study of local radiation therapy may be via proton beam irradiation or stereotactic radiotherapy. Several intravitreal injections are being studied including human immuno-conjugate molecule (hl-con1), abicipar pegol, PF582, DE-120, ESBA 1008, and REGN2176-3. SUMMARY: Numerous treatment options of neovascular age-related macular degeneration are in phase 1/2 clinical trials including gene therapy, eye drops, systemic dosing, localized irradiation, and various intravitreal injections. Future phase 3 trial results will be observed closely to determine which of these therapies will be the next novel treatment of neovascular age-related macular degeneration.

Single Institution Experience of Intravitreal 0.18-mg Fluocinolone Acetonide Implant for Noninfectious Uveitis.

PURPOSE: To report the outcomes of the 0.18-mg fluocinolone acetonide implant (FAi) in the treatment of noninfectious uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients who received the 0.18-mg FAi for the treatment of noninfectious uveitis affecting the posterior segment (NIU-PS) between July 1, 2019, and August 31, 2021, at the University of Colorado. Patients were excluded if they did not have ≥ 6 months of follow-up after the placement of the implant. METHODS: Data including age, race/ethnicity, sex, uveitis diagnosis, history and current use of anti-inflammatory therapy, use of short-acting corticosteroid injections within the 3 months before the 0.18-mg FAi implantation, visual acuity, intraocular pressure (IOP), grading of anterior chamber and vitreous cell, and presence of cystoid macular edema were obtained from the medical charts. Uveitis recurrence was defined as any increased inflammation that required additional anti-inflammatory therapy. MAIN OUTCOME MEASURES: Probability of remaining recurrence-free after the placement of the 0.18-mg FAi. RESULTS: Sixty-four eyes from 42 patients were included. The overall probability of remaining recurrence-free was 68.8% at 6 months and 52.6% at the 12-month follow-up. Eyes that remained recurrence-free at 12 months had a younger mean age than eyes that had a recurrence within 12 months (P = 0.02). Eyes that received a short-acting corticosteroid injection before the 0.18-mg FAi were more likely to have a recurrence by 6 months of follow-up than eyes that did not receive a pre-FAi corticosteroid injection (P = 0.05). Initiation or addition of IOP-lowering eyedrops was required in 15.6% of eyes, and 4.7% of eyes required IOP-lowering surgery after 0.18-mg FAi placement. CONCLUSIONS: The 0.18-mg FAi appears to be an effective option in the management of NIU-PS, with relatively low rates of ocular hypertension requiring intervention. The use of short-acting corticosteroid injections before the placement of the 0.18-mg FAi does not seem to improve the effectiveness of the 0.18-mg FAi, although this may be partially because of selection bias. Additional studies are required to determine patients who are the optimal candidates for this therapy.

The Clinical Characteristics of Noninfectious Occlusive Retinal Vasculitis.

PURPOSE: To characterize the clinical features of occlusive retinal vasculitis (ORV). DESIGN: Retrospective case series. PARTICIPANTS: Forty-two patients with ORV. METHODS: A retrospective chart review identified all patients with ORV seen at the University of Colorado uveitis service between January 2013 and April 2020. All included patients demonstrated noninfectious uveitis and evidence of vascular occlusion in the presence of retinal vascular inflammation on widefield fluorescein angiography. MAIN OUTCOME MEASURES: Demographic data, visual acuity, clinical findings, and fluorescein angiography findings. RESULTS: We identified 73 eyes from 42 patients (15 men, 27 women) with ORV. Thirty-one of 42 patients had bilateral disease. Most eyes (54/73) showed mixed arteriolar and venous vasculitis compared with primarily arteriolar (6/73) or venous (15/73) vasculitis. Thirteen of 42 patients had an underlying systemic condition, most commonly granulomatosis with polyangiitis; however, bilaterality was not associated with a systemic condition. Retinal nonperfusion was present equally in zone 2 (28/73) and zone 3 (28/73) compared with zone 1 (16/73). Retinal or iris neovascularization was present in 25 of 73 eyes. Eighteen of 42 patients required more than 1 immunosuppressive medication (average, 1.33) to prevent progressive vascular occlusive disease. CONCLUSIONS: Occlusive retinal vasculitis is a heterogeneous entity with significant risk of visual impairment. Systemic disease was more prevalent in this specific cohort compared with cohorts from prior studies of retinal vasculitis.

PURTSCHER'S‒LIKE RETINOPATHY SECONDARY TO GRANULOMATOSIS WITH POLYANGIITIS FOLLOWING AUTOLOGOUS STEM CELL TRANSPLANTATION.

PURPOSE: The authors describe a man undergoing autologous stem cell transplant, who developed granulomatosis with polyangiitis and Purtscher's‒like retinopathy. METHODS: A 25-year-old man underwent fundus photography, optical coherence tomography, and fluorescein angiography to obtain a diagnosis and follow the treatment course. RESULTS: The initial ophthalmic presentation and imaging confirmed the findings of Purtscher's‒like retinopathy. Throughout his course, he had progressive neovascularization and vitreous hemorrhages in both eyes, requiring vitrectomy and endolaser, and bevacizumab injections. CONCLUSION: The authors describe a patient who underwent autologous stem cell transplantation, and subsequently developed granulomatosis with polyangiitis. The presentation of Purtscher's‒like retinopathy suggests that microvascular occlusion in the retina was likely the result of granulomatosis with polyangiitis-driven vasculitis of the precapillary arterioles.

Evaluation of the SUN Classification Criteria for Uveitides in an Academic Uveitis Practice.

PURPOSE: To evaluate the new Standardization of Uveitis Nomenclature (SUN) classification criteria for uveitides by applying them to patients in an academic uveitis practice. DESIGN: Evaluation of classification criteria. METHODS: The charts of all patients attending the uveitis service at the University of Colorado Hospital between January 1, 2013, and December 31, 2020, were reviewed. Patients with scleritis, ocular cicatricial pemphigoid, and peripheral ulcerative keratitis were excluded. We attempted to classify each patient's uveitis using the SUN classification criteria. Classification attempts were made within the relevant anatomical or infectious categories for their pathology but did not necessarily have to match their clinical diagnosis by a uveitis specialist. We recorded whether classification was possible as well as their clinical diagnosis by a uveitis specialist. RESULTS: All patients attending the uveitis clinic at our academic institution between January 1, 2013, and December 31, 2020, were reviewed. Of the 1143 patients with uveitis, 572 (50.0%) had a disease that was not listed in the SUN classification system, and so no attempt to classify these patients was possible. Of the remaining 571 patients, 522 (91.4%) were able to be classified by SUN and in 492 (94.3%) of the 522 cases, their SUN classification matched their clinical diagnosis by a uveitis specialist. CONCLUSIONS: Half of the patients at an academic uveitis practice had a disease for which no SUN classification criteria existed. In cases where classification by SUN could be attempted, the system performed well and generally agreed with their clinical diagnosis.

Quantitative effect of subretinal fluid and intraretinal edema on visual acuity in uveitic cystoid macular edema.

BACKGROUND: The effect of subretinal fluid (SRF) in uveitic cystoid macular edema (CME) is not fully understood. This study evaluates the quantitative effect of SRF and intraretinal thickness on visual acuity in eyes with uveitic CME. We separately measured SRF and intraretinal area on Optical Coherence Tomography (OCT) to determine the associations of each component with visual acuity and response to treatment. MAIN TEXT: Medical records were reviewed of patients with CME presenting to the University of Colorado uveitis clinic from January 2012 to May 2019. All available OCTs were reviewed to classify eyes as either having only CME or CME with SRF. Intraretinal area was manually measured using Image J along the central 1-mm section of B-scan OCT spanning from the internal limiting membrane to the outer most portion of the outer retina including both cysts and retinal tissue. SRF cross-sectional area was measured spanning from the outermost portion of the outer retina to retinal pigment epithelium. Response to treatment was assessed one to four months after presentation. Eyes with CME secondary to structural or non-inflammatory causes were excluded. Forty-seven (50.5%) eyes had CME alone and 46 (49.5%) eyes had SRF with CME. Measured SRF cross-sectional area was not associated (p = 0.21) with LogMAR at presentation. Conversely, intraretinal area was strongly correlated with visual acuity in eyes with SRF (p < 0.001) and without SRF (p < 0.001). Following treatment, there was a significant decrease in intraretinal area for both groups (p < 0.001), with a larger decrease in the SRF group compared to the non-SRF group (p = 0.001). Similarly, logMAR improved in both groups (p = 0.008 for SRF eyes and p = 0.005 for non-SRF eyes), but the change was more prominent in the SRF group (p = 0.06). CONCLUSIONS: There was no direct association observed between the amount of SRF and visual acuity. In contrast, increased intraretinal area was significantly associated with decreased visual acuity. This relationship between intraretinal thickening and visual acuity may explain differences observed in response to treatment between SRF and non-SRF eyes, with a larger decrease in the intraretinal cross-sectional area in SRF eyes associated with a greater improvement in logMAR visual acuity.

The impact of advanced age-related macular degeneration on the National Eye Institute's Visual Function Questionnaire-25.

PURPOSE: To assess visual function among patients diagnosed with age-related macular degeneration (AMD) by stage of disease and laterality. METHODS: This is a cross-sectional cohort study of 739 AMD patients and their responses to the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) at time of study enrolment. Patients with AMD were categorized into Early/Intermediate AMD and three groups of advanced AMD: (i) neovascular AMD (NV), (ii) geographic atrophy (GA) and (iii) Both Advanced forms. These three advanced stages were further stratified into unilateral or bilateral advanced disease. Mean composite scores and subscale scores for 12 different areas were based on a 100-point scale with the lowest and highest possible scores set at 0 and 100, respectively. Scores for the advanced AMD groups were compared with Early/Intermediate AMD using general linear modelling. RESULTS: A total of 739 AMD patients (294 Early/Intermediate, 115 GA, 168 NVAMD and 162 Both Advanced) were included in the analysis. Mean composite scores were highest among Early/Intermediate patients (89.9), followed by patients diagnosed with unilateral disease in the Both Advanced (88.0) and NV (86.1) groups. Mean composite scores were similar for bilateral NV (82.9) and unilateral GA (81.7), and mean scores were lowest for the bilateral GA (71.3) and bilateral Both Advanced (68.5) groups. In general, this pattern persisted across the twelve subscales as well. Subscale scores ranged from a low of 35.1 for driving among bilateral Both Advanced patients to a high of 99.2 for colour vision among patients with unilateral Both Advanced. Overall, patients with unilateral advanced disease consistently had higher mean scores than their bilateral counterparts. The largest difference was 19.5 composite score points between the unilateral and bilateral Both Advanced groups, there was a difference of 10.4 points between the GA groups, and a relatively small difference of 3.2 points between the NV groups. CONCLUSIONS: We found large differences in visual function as reported from the VFQ-25 across the different types of advanced stage AMD groups and number of eyes affected with advanced AMD. These findings demonstrate the importance of accounting for the type and number of eyes affected by advanced stage AMD.

Outcomes and Complications Associated with Noninfectious Uveitis in Patients Presenting with Rhegmatogenous Retinal Detachment.

PURPOSE: To evaluate the visual outcomes and complications associated with noninfectious uveitis in patients presenting with a rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 554 eyes of 523 patients presenting for RRD repair at the Department of Ophthalmology, University of Colorado School of Medicine, between July 2011 and September 2016. METHODS: Analysis of risk factors, anatomic outcomes, and visual outcomes related to a history of noninfectious uveitis. MAIN OUTCOME MEASURES: End point rate of reattachment, end point visual acuity (VA), postoperative proliferative vitreoretinopathy (PVR), and rate of reoperation. RESULTS: A history of uveitis was identified in 5.4% of eyes. Eyes with a history of uveitis were found to have a higher risk for development of any degree of PVR (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.1-4.4, P = 0.030) and a higher risk of PVR necessitating an additional procedure (HR, 2.7; 95% CI, 1.2-6.0, P = 0.014). Anatomic and visual outcomes did not differ between the 2 groups. Preoperative VA, the distribution of race/ethnicity, age, gender, lens status, macula status, and lattice degeneration status did not vary significantly between the groups. In the analysis of a PVR subgroup, uveitis was not associated with a higher risk of PVR necessitating an additional procedure and did not show a statistically significant difference in end point VA. CONCLUSIONS: A history of uveitis is associated with an increased risk of any degree of PVR and an increased risk of PVR necessitating an additional procedure. However, subgroup analysis suggests that patients with a history of uveitis who develop PVR do not necessarily have a worse visual outcome or a higher risk of additional surgery. There may be a role for perioperative steroids in patients with a history of uveitis who present with a retinal detachment, but further study is warranted to determine if this decreases the risk of PVR or improves visual outcomes.

Chest X-ray and Uveitis Evaluation in a Population with Low Incidence of Sarcoidosis.

INTRODUCTION: Radiographic chest imaging is utilized in the workup of uveitis, with the purpose of diagnosing sarcoidosis. Sarcoidosis is an idiopathic systemic granulomatous inflammation which accounts for approximately 10% of uveitis. The prevalence of sarcoidosis and uveitis varies widely with geography and ethnicity. We studied the value of chest X-ray (CXR) in the evaluation of uveitis patients in the Western United States. The study was a retrospective chart review of 559 patients presenting to the Uveitis Department at University of Colorado between January 1, 2011 and July 31, 2017. METHODS: CXR and/or chest computerized tomography (CT) was obtained in patients with an unknown uveitic diagnosis. Presumed sarcoidosis was defined as the presence of bilateral hilar lymphadenopathy in a patient with uveitis. Age, race, and anatomic location of the uveitis were analyzed. RESULTS: The prevalence of sarcoidosis in our population was 4.3%. The discovery rate of sarcoidosis by CXR was 2.6%. Of 12 positive CXRs, 11 were in black patients. Our study identified five previously undiagnosed patients with sarcoidosis, four of whom were black. CONCLUSIONS: CXR screening for sarcoid uveitis has a low yield in our population and is most likely to be positive in black patients. The prevalence of sarcoidosis is low in our study but not unlike the findings in similar demographic populations. Although chest CT scan is more sensitive than chest X-ray, the cost and radiation dose are greater; thus CT may not be indicated in low incidence populations.

Indicators of Post-Operative Intraocular Pressure Elevation after Naïve Fluocinolone Acetonide Surgical Implantation.

PURPOSE: To determine factors conferring an increased risk of developing ocular hypertension secondary to the fluocinolone acetonide (FA) sustained-release surgical implant (Retisert). DESIGN: Retrospective, observational case series. METHODS: Patients with a history of chronic noninfectious posterior uveitis undergoing naïve surgical FA implantation from 2007 to 2018 at the University of Colorado were studied. Patient demographics and multiple clinical measures were noted one year before and after FA implantation. RESULTS: Twenty-nine eyes of 21 patients were studied. The median age experiencing an IOP rise vs median age experiencing no IOP rise post-FA implantation was 27.0 and 54.0 years old, respectively (p = .01). A pre-FA implant risk factor of needing future glaucoma surgery after FA implantation is prior to maximum IOP (p = .02). CONCLUSIONS: A risk factor of elevated post-FA implantation IOP includes younger age. A potential risk factor for glaucoma surgery after FA implantation was higher maximum IOP before FA implantation.

Current Best Clinical Practices-Management of Retinal Vein Occlusion.

Retinal vein occlusion (RVO) is the second most common cause of vision loss from retinal vascular diseases in adults in the United States. Visual loss arises as a result of a host of factors, including macular ischemia and macular edema. Primary antivascular endothelial growth factor therapy is the current standard of care, with level I evidence demonstrating sustained visual gains up to 2 years after treatment in both branch and central RVO. Prompt antivascular endothelial growth factor therapy is important because delays in treatment yield lesser visual gains. Steroid therapy also improves visual outcomes in RVO but with higher rates of adverse effects, including cataract formation and ocular hypertension. Although the treatment burden can be high, these drugs have collectively revolutionized treatment outcomes in this disease state, providing improved visual outcomes over previous laser therapies.

A Cross-Sectional Online Survey Identifies Subspecialty Differences in the Management of Pediatric Cataracts Associated with Uveitis.

INTRODUCTION: To determine if differences exist between pediatric ophthalmologists and uveitis ophthalmologists in the treatment of pediatric uveitic cataracts and placement of intraocular lenses. METHODS: Uveitis ophthalmologists and pediatric ophthalmologists were surveyed via an online poll regarding their therapeutic management of pediatric uveitic cataract and intraocular lens (IOL) placement. RESULTS: Sixty-two responses from uveitis ophthalmologists and 47 responses from pediatric ophthalmologists were recorded. According to 79% of all responses, uveitis was not a contraindication for primary IOL implantation in patients with controlled intraocular inflammation. Pediatric ophthalmologists were more likely to respond that the presence of chronic juvenile idiopathic arthritis-associated iridocyclitis, pars planitis, or recurrent acute anterior uveitis is a contraindication for primary IOL implantation in pediatric cases with full control of intraocular inflammation. There was no consensus within either specialty with regard to the preferred IOL material for lens implantation. Uveitis ophthalmologists were more likely to report the use of intravenous and intravitreal steroids for perioperative treatment. In cataract surgery for a child with recurrent acute anterior uveitis, a higher percentage of uveitis ophthalmologists (71%) than pediatric ophthalmologists (50%) responded that the posterior capsule should be primarily opened. A higher percentage of uveitis ophthalmologists also stated that anterior vitrectomy should be performed at the time of cataract surgery in all three uveitis types. CONCLUSIONS: Pediatric ophthalmologists and uveitis ophthalmologists have similar approaches to the management of pediatric uveitic cataract removal and IOL insertion, but several differences remain between these subspecialties. Continued collaboration between the subspecialties would be helpful to better develop consistent criteria to improve patient care.

AIDS-related Cryptococcus neoformans choroiditis.

We describe a case of Cryptococcal choroiditis in a person with advanced HIV/AIDS. A 29-year-old male with AIDS presented with fever, photophobia, and ataxia secondary to cryptococcal and toxoplasma meningoencephalitis. Dilated fundoscopic examination revealed bilateral and multifocal posterior infiltrates consistent with cryptococcal choroiditis. Treatment with parenteral and intravitreal liposomal amphotericin B, oral flucytosine, and oral trimethoprim-sulfamethoxazole led to resolution of his symptoms and improvement in his vision. Our case documents a rare, intraocular opportunistic infection and highlights the importance of ophthalmologic examination in immunocompromised hosts with visual symptoms and invasive fungal infection. We discuss diagnostic and treatment considerations in cryptococcal choroiditis.

Ophthalmic medication price variation across the United States: Anti-inflammatory medications.

BACKGROUND: Cost-related nonadherence to medication can impact ophthalmic treatment outcomes. We aimed to determine whether medication prices vary between US cities and between different types of pharmacies within one city. METHODS: We conducted a phone survey of eight nationwide and five independent pharmacies in five cities across the United States: Boston, Massachusetts; Charlotte, North Carolina; Denver, Colorado; Detroit, Michigan; and Seattle, Washington. A researcher called each pharmacy asking for price without insurance for four common anti-inflammatory ophthalmic medications: prednisolone acetate, prednisolone sodium phosphate, difluprednate (Durezol™), and loteprednol etabonate (Lotemax™). RESULTS: Prednisolone sodium phosphate price could only be obtained by a small subset of pharmacies (45.2%) and was excluded from additional analysis; however, preliminary data demonstrated lower cost of prednisolone sodium phosphate over prednisolone acetate. Three-way analysis of variance revealed no interaction between pharmacy type (chain versus independent), city, and drug (F = 0.40, p = 0.92). A significant interaction was identified between pharmacy type and drug (F = 5.0, p = 0.008), but not city and pharmacy type (F = 0.66, p = 0.62) or city and drug (F = 0.27, p = 0.97). Average drug prices were lower at independent pharmacies compared with chain pharmacies for difluprednate (US$211.36 versus US$216.85, F = 1.09, p = 0.297) and significantly lower for loteprednol etabonate (US$255.49 versus US$274.86, F = 14.7, p < 0.001). Prednisolone acetate was cheaper at chain pharmacies, but not statistically significantly cheaper (US$48.82 versus US$51.61, F = 0.34, p = 0.559). CONCLUSIONS: Medication prices do not differ significantly between US cities. High variation of drug prices within the same city demonstrates how comparison shopping can provide cost savings for patients and may reduce cost-related nonadherence.

Inflammatory side effects of BRAF and MEK inhibitors.

The aim of this study was to describe inflammatory side effects in patients treated with BRAF and MEK inhibitors at a single tertiary care institution. This was a retrospective chart review of patients prescribed single-agent or combination BRAF and MEK inhibitors from January 2010 until May 2015. The primary outcome was the presence of inflammatory side effects. Among 124 patients, 56.4% were male, the median age was 59 years, and most (91.1%) were treated for metastatic melanoma. Most patients (74.2%) developed inflammatory side effects, some with multiple occurrences, for a total of 211 occurrences. The overall prevalence of inflammatory side effects did not differ across therapies. In a subanalysis, patients treated with both single-agent and combination therapies were more likely to experience an inflammatory side effect on single-agent therapy (P = 0.0126 for BRAF inhibitor, P = 0.0833 for MEK inhibitor). The most common inflammatory side effects for the entire cohort included arthralgias/myalgias (32.9%), nonacneiform rash (28.0%), pyrexia (25.5%), and erythema nodosum (11.2%), although side effects differed across the class of therapy. Corticosteroids were initiated in 73 side effect instances among 47 patients. Drug interruption or dose reduction was reported in 78 side effect instances in 50 patients. Fifteen side effect instances led to treatment termination. There is a high prevalence of inflammatory side effects encompassing all organ systems in patients treated with BRAF and MEK inhibitors. There is no significant difference in the prevalence of inflammatory side effects in patients treated with single-agent versus combination therapies, however, side effect profile differs across agents.