Acute central corneal haze and thinning with atypical keratitis presentation.

A 24-year-old woman presented with a 7-day history of blurry vision, redness, and extreme pain in her right eye. She had no pertinent medical or ocular history and did not use spectacles or contacts. Uncorrected distance visual acuity (UDVA) was 20/40 in the right eye and could not be improved with refraction. Slitlamp examination revealed a 1.5 × 1.5 mm central epithelial defect with surrounding white blood cell recruitment. Confocal microscopy (Figure 1JOURNAL/jcrs/04.03/02158034-202304000-00020/figure1/v/2023-03-24T200747Z/r/image-tiff) was performed, and she was treated with chlorhexidine 0.02% drops every hour in the right eye. 2 weeks later, the cornea had completely re-epithelialized; however, persistent corneal haze, decreased visual acuity, and corneal thinning and flattening was noted. Pachymetry was 484 µm in the right eye and UDVA was 20/40 (Supplemental Figure 1, available at http://links.lww.com/JRS/A836). In the following 2 weeks, UDVA improved to 20/25. 6 months after the initial presentation, UDVA was unchanged and faint central corneal haze was noted on examination (Figure 2JOURNAL/jcrs/04.03/02158034-202304000-00020/figure2/v/2023-03-24T200747Z/r/image-tiff). Of interest, her family history is significant for her younger 16-year-old brother with 3 prior episodes of a similar type of keratitis/keratopathy over the course of 2 years in both eyes with similar central paracentral corneal haze, thinning, and flattening and similar confocal findings (Figure 3JOURNAL/jcrs/04.03/02158034-202304000-00020/figure3/v/2023-03-24T200747Z/r/image-tiff). He also was unresponsive to topical antibiotics and antivirals except topical chlorhexidine. Her brother has been our patient for the last several years prior to her first visit to our clinic. What is your diagnosis? What medical diagnostic tests, if any, would you recommend? Is this an infectious or simply an inflammatory response? Is there any genetic or familial predisposition?

Contrasting presentations of the same disease: A comparison of two cases of amyloidosis presenting with eyelid involvement.

Purpose: Localized amyloidosis can affect numerous tissues throughout the body and can also affect a variety of peri-ocular tissues including the conjunctiva, extra-ocular muscles, peri-orbital soft tissue, and lacrimal gland. We report two cases of amyloidosis presenting with eyelid involvement. Observations: The first case represented a more subtle presentation of skin thickening with a pre-septal cellulitis, while the second case had a dramatic presentation of edema evolving into tissue dehiscence and spontaneous hemorrhage with ongoing angioedema and systemic coagulopathy. Conclusions and importance: The two cases of biopsy-proven orbital/peri-ocular amyloidosis demonstrate the different clinical presentations that may go from the subtle to dramatic, depending on which peri-ocular tissues are affected and to what degree. Standards for treatment of amyloidosis remain conservative initially with surgery or radiation recommended only for refractory cases, but additional therapies are under investigation. Clinicians should have high clinical suspicion for amyloidosis with findings such as skin thickening or significant periorbital edema and should always consider tissue biopsy and further workup for amyloidosis if the findings worsen or do not resolve with treatment of more common conditions such as cellulitis.

Pachymetric Assessment After EpiSmart® Epithelium-on Cross-Linking for Keratoconus and Post-Surgical Ectasia.

Purpose: To assess the change in corneal pachymetry after a novel epithelium-on (EpiSmart®) corneal crosslinking procedure (CXL). Methods: Eyes treated as part of the open-label, non-controlled arm of the study "Collagen Crosslinking with Ultraviolet-A in Asymmetric Corneas" (NCT01097447) were examined at baseline, 3-, 6- and 12-months post-CXL. Thinnest pachymetry readings based on Pentacam (OCULUS GmbH, Wetzlar, Germany) were recorded. Results: A total of 101 eyes met the study inclusion criteria. Thinnest pachymetric readings at baseline averaged 451 ± 50 microns. The mean (± SD) minimum thickness was 450 ± 46 microns at 3 months, 452 ± 47 microns at 6 months, and 451 ± 48 microns at 12 months post-CXL. The changes from baseline (mean ± SE) at 3, 6, and 12 months post-CXL were -1.2 ± 1.5 microns, 0.5 ± 1.6 microns, and 0.4 ± 1.6 microns, respectively. Student's t-tests showed no statistically significant change in pachymetry from baseline for any exam period. Conclusion: This study demonstrated that, after EpiSmart® epithelium-on CXL, there was no substantial corneal thinning observable on Scheimpflug tomography out to 12 months.

Fungal Infectious Interface Keratitis Presenting 2 Years After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: The purpose of this study was to describe infectious interface keratitis after Descemet membrane endothelial keratoplasty (DMEK) more than 2 years after surgery. METHODS: A case study. RESULTS: In this study, we report a case of fungal infectious interface keratitis occurring 2 years after uncomplicated Descemet membrane endothelial keratoplasty. The donor corneal rim culture at the time of surgery grew a single colony of Candida albicans/dubliniensis , but the patient was not treated with antifungals at that time. At the onset of clinical infection, more than 2 years postoperatively, the patient was treated with systemic antifungals and adjuvant intrastromal amphotericin-B injection. The patient subsequently required penetrating keratoplasty with ultimately well-preserved visual acuity. CONCLUSIONS: Fungal infectious interface keratitis (IIK) is a rare complication associated with lamellar keratoplasty. Although most common in the early postoperative period, this complication can occur several years after successful transplantation. Management may require a combination of systemic and stromal antifungal therapy. However, some patients may eventually require penetrating keratoplasty for definitive treatment.

KPI-121 1% for pain and inflammation in ocular surgery.

Pain and inflammation are common experiences following ocular surgery and, if uncontrolled, can compromise patients' vision, functioning and quality of life. Corticosteroid drugs are available to manage inflammation and discomfort but have limitations in penetrating the ocular mucus barrier to reach the target ocular tissues. KPI-121 1% (INVELTYS®) is a novel formulation of loteprednol etabonate that employs innovative proprietary technology to deliver nanoparticle-sized mucus-penetrating particles to the cornea. Results from clinical trials demonstrate that KPI-121 1% is effective and well tolerated. KPI-121 1% uses mucopenetrative technology for ophthalmic use and is the only US FDA-approved twice-daily ocular corticosteroid indicated for the treatment of inflammation and pain after ocular surgery.

Persistence, Dose Titration, and Health Care Resource Utilization Among Crohn's Disease Patients Treated With Ustekinumab: A Real-World Analysis in the United States.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. This real-world study evaluated persistence, dose titration, health care resource utilization (HCRU) and associated costs, and medication use among CD patients treated with ustekinumab (UST) in several pooled US commercial database populations. METHODS: CD patients aged ≥ 18 years with medical or pharmacy claims for UST were selected from pooled data from 3 large, national commercial databases. The first observed medical or pharmacy claim for UST was the index date. Patients were required to have had ≥ 1 medical claim with a CD diagnosis during the 12 months prior to the index date and continuous health plan enrollment for a minimum of 12 months prior to and 12 months after the index date. Comparisons of outcomes during the baseline and follow-up periods were conducted using inferential statistical tests. RESULTS: A total of 214 eligible UST patients were selected. The majority (74.8%) were biologic experienced (mean age: 41 years), and 83.6% remained treatment persistent during the 12-month post-index period. Among discontinuers, 25.7% restarted UST, and 8.6% switched from UST in the 12-month observation period. The mean treatment duration was 329 days. Most patients (77%) used the recommended UST dose, as defined as being within a 20% dose variation from label (90 mg/8 weeks ± 20%), 17.9% experienced dose escalation, and 5.1% experienced dose reduction. Post-index immunomodulator and corticosteroid use reduced by 20% and 28%, respectively, as compared with pre-index use among CD patients using UST. Annual all-cause ER visits and inpatient stays decreased by 20.5% and 30.3%, respectively, with similar downward trends for annual CD-related HCRU. CONCLUSIONS: The majority of CD patients prescribed UST were biologic experienced, and persistence was high over the 1-year follow-up. UST treatment initiation was associated with reductions in ER visits, inpatient stays, and steroid and other medication use.

Hypoglycaemia and treatment patterns among insulin-treated patients with type 2 diabetes who switched to insulin glargine 300 units/mL versus other basal insulin in a real-world setting.

INTRODUCTION: Type 2 diabetes (T2D) is characterized by worsening pancreatic ß-cell function often requiring treatment escalation with oral antidiabetic drugs (OADs), glucagon-like peptide-1 and eventually insulin. Although there is much evidence available on the initiation of basal insulins, fewer studies have investigated the effects of switching from one basal insulin to another. This study aims to evaluate treatment persistence and hypoglycaemia in adult patients with T2D on prior basal insulin who were switched to insulin glargine 300 units/mL (Gla-300) or other basal insulins in a real-world setting. MATERIALS AND METHODS: This study is a retrospective cohort analysis of patient-level data extracted from the Optum® Clinformatics™ database between 1 October 2014 and 30 June 2016. Adult patients (≥18 years) with T2D who were being treated with basal insulin during the 6-month baseline period, who switched to either Gla-300 or other basal insulins, were followed up for ≥3 months after switching. Outcomes included treatment persistence, and incidence and number of hypoglycaemic events. RESULTS: Of the included patients, 1204 switched to Gla-300 and 616 switched to other basal insulins. Adjusting for baseline confounders, patients who switched to Gla-300 were 34% less likely to discontinue their basal insulin than patients who switched to other basal insulins (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.54-0.81; P < 0.001). Patients who switched to Gla-300 were less likely to experience hypoglycaemia at 3-month follow-up (odds ratio [OR] 0.56, 95% CI 0.32-0.97; P = 0.039) and at 6-month follow-up (OR 0.58, 95% CI 0.38-0.87; P = 0.009) compared with patients who switched to other basal insulins. CONCLUSIONS: Patients with T2D on prior basal insulin in a real-world setting who switched to Gla-300 were more persistent with their basal insulin and experienced less hypoglycaemia than patients who switched to other basal insulins.

Patients with Idiopathic Membranous Nephropathy: A Real-World Clinical and Economic Analysis of U.S. Claims Data.

BACKGROUND: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in nondiabetic adults. Approximately one third of patients with MN progress to end-stage renal disease (ESRD), while others may be successfully treated to remission. Patients with MN represent a high-risk population for whom management strategies can alter and improve outcomes. Currently, there is little real-world evidence regarding the burden of MN on health plans. OBJECTIVES: To (a) characterize clinical and economic outcomes during a 1-year time frame among a prevalent cohort of patients with MN and (b) compare the 5% of patients incurring the highest cost with the remaining 95%. METHODS: A retrospective analysis of commercially insured patients was conducted using MarketScan administrative health care claims data from January 1, 2012, to December 31, 2015. Patients were aged ≥ 18 years, enrolled In a fee-for-service plan, and had ≥ 2 medical claims for an MN diagnosis (ICD-9-CM codes 581.1, 582.1, and 583.1). Diagnoses indicating clear secondary causes were excluded wherever possible. Demographics were determined as of the first diagnosis date; clinical characteristics (e.g., MN-specific therapy, complications, and procedures), health care resource utilization (HCRU; inpatient, outpatient including other outpatient and emergency department [ED], and prescriptions), and costs were evaluated for 1 year following MN diagnosis. Total costs and cost distribution (2017 U.S. dollars) were examined using plan-paid and patient-paid amounts. The 95th percentile was used to categorize and compare the subcohorts: high-cost cohort (HCC) patients (top 5%) and non-high-cost cohort (NHCC) patients (the remaining 95%). Descriptive analyses, chi-square tests, and Wilcoxon rank-sum tests were conducted. RESULTS: 2,689 patients were identified (60.0% male, mean age = 46.4 years). Severity and advanced disease were observed In a higher proportion of HCC patients (n = 134) versus NHC patients (n = 2,555) via adverse health outcomes, procedures, and immunosuppressant use. HCC patients used significantly more resources on average than NHCC patients (additional use): 1.7 inpatient, 1.2 ED, and 4.8 outpatient office visits; 15 prescriptions; and 64.8 other outpatient visits (i.e., outpatient, hospital, and ESRD facilities). Total MN-related cost and mean (SD) cost per patient were $123.2 million and $45,814 ($101,353); HCC patients accounted for 43.7% of total costs for a mean cost per patient of $401,608 versus NHCC patients at 56.3% and mean cost per patient of $27,154. The greatest costs for both groups were related to outpatient visits (HCC = 46.7%; NHCC = 52.8%), inpatient visits (HCC = 27.7%; NHCC = 28.6%), and prescriptions (HCC = 25.7%; NHCC = 18.6%). CONCLUSIONS: Patients with MN are significantly burdened with high disease severity and adverse health outcomes, resulting In substantial HCRU and costs. Health plan cost drivers for MN (HCC and NHCC patients) occurred primarily In the outpatient setting, followed by the inpatient setting and prescriptions. Modifiable aspects preceding progression to advanced renal disease and worse outcomes should be explored to Identify effective interventions and improve resource allocation earlier In the disease pathway, before ESRD. DISCLOSURES: This study was funded by Mallinckrodt Pharmaceuticals. Kirkemo, Pavlova-Wolf, and Bartels-Peculis are employees and stockholders of Mallinckrodt Pharmaceuticals. Nazareth was an employee of Mallinckrodt Pharmaceuticals at the time of this study. Kariburyo, Xie, and Vaidya are employees of STATinMED Research, a paid consultant to Mallinckrodt Pharmaceuticals. Sim received an investigator-initiated research grant from Mallinkcrodt Pharmaceuticals. A portion of the study results were previously presented at the American Society of Nephrology (ASN) Kidney Week 2017; November 2, 2017; New Orleans, LA.

Evaluating the Effect of Treatment Persistence on the Economic Burden of Moderate to Severe Psoriasis and/or Psoriatic Arthritis Patients in the U.S. Department of Defense Population.

BACKGROUND: Psoriasis is a chronic, hyper-proliferative dermatological condition associated with joint symptoms known as psoriatic arthritis (PsA). In a 2013 review, the total economic burden of PsA was estimated at $51.7-$63.2 billion. The economic burden of moderate to severe psoriasis patients has reduced significantly with the advent of biologics, but there remains a dearth of real-world evidence of the impact of treatment persistence on the economic burden of moderate to severe psoriasis and/or PsA patients. OBJECTIVE: To evaluate the overall and psoriasis and/or PsA-related health care utilization and costs among patients who were persistent versus those nonpersistent on index biologic among the moderate to severe psoriasis and/or PsA population. METHODS: Adult patients with ≥ 2 claims with diagnosis of psoriasis and/or PsA during the period of November 2010-October 2015 were identified from the U.S. Department of Defense database; the first diagnosis date during November 2011-October 2014 was defined as the index date. As of the index date, patients were considered to have moderate to severe psoriasis or PsA if they had ≥ 1 nontopical systemic therapy or phototherapy during the 1-year pre- or 1-month post-index date. Persistence to index therapy, defined as the first biologic used (etanercept, adalimumab, ustekinumab, infliximab) on or within 30 days post-index date, was determined based on the biologic dosing schedule and a 90-day gap. Generalized linear models were used to compare the health care utilization and costs between persistent and nonpersistent patients during the 1-year post-index period. RESULTS: A total of 2,945 moderate to severe psoriasis and/or PsA patients were identified. Of those, 1,899 (64.5%) were persistent and 1,046 (35.5%) were nonpersistent. Compared with nonpersistent patients, persistent patients were older (49.2 vs. 45.5 years; P < 0.001) and more likely to be male (52% vs. 45%; P < 0.001). More persistent patients were diagnosed with dyslipidemia (40% vs. 35%; P = 0.002), had lower antidepressant use (23.4% vs. 27.4%; P < 0.001), and had lower anxiolytic use (30% vs. 37%; P < 0.001) compared with nonpersistent patients. After adjusting for demographic and clinical characteristics, nonpersistent patients had higher total medical costs ($12,457 vs. $8,964; P < 0.001) compared with persistent patients, and ambulatory visits (23.9 vs. 21.4; P = 0.007) were a major contributor. Approximately 40% of the total overall medical costs were attributed to psoriasis and PsA. Although persistent patients incurred higher pharmacy costs ($10,684 vs. $7,849; P < 0.001) due to higher biologic use and the potentially high per-unit cost of biologics, their psoriasis- and/or PsA-related medical costs were significantly lower than those of nonpersistent patients ($3,395 vs. $5,041; P < 0.001). Total overall costs combining medical and pharmacy costs were similar between the cohorts ($22,678 vs. $21,477; P = 0.122). CONCLUSIONS: Moderate to severe psoriasis and/or PsA patients who were persistent on index biologic treatment had higher pharmacy utilization and costs, albeit with lower medical costs and similar total costs, compared with nonpersistent patients. DISCLOSURES: This study was funded by Janssen Scientific Affairs. Lee is a paid employee of Janssen Scientific Affairs. Xie, Wang, Vaidya, and Baser are paid employees of STATinMED Research, which is a paid consultant to Janssen Scientific Affairs. This study was presented as an abstract at the Academy of Managed Care Pharmacy 2017 Annual Meeting, March 27-30, 2017, in Denver, CO.

Comorbidity and economic burden among moderate-to-severe psoriasis and/or psoriatic arthritis patients in the US Department of Defense population.

AIMS: To examine the comorbidity and economic burden among moderate-to-severe psoriasis (PsO) and/or psoriatic arthritis (PsA) patients in the US Department of Defense (DoD) population. MATERIALS AND METHODS: This retrospective cohort claims analysis was conducted using DoD data from November 2010 to October 2015. Adult patients with ≥2 diagnoses of PsO and/or PsA (cases) were identified, and the first diagnosis date from November 2011 to October 2014 was defined as the index date. Patients were considered moderate-to-severe if they had ≥1 non-topical systemic therapy or phototherapy during the 12 months pre- or 1 month post-index date. Patients without a PsO/PsA diagnosis during the study period (controls) were matched to cases on a 10:1 ratio based on age, sex, region, and index year; the index date was randomly selected. One-to-one propensity score matching (PSM) was conducted to compare study outcomes in the first year post-index date, including healthcare resource utilization (HRU), costs, and comorbidity incidence. RESULTS: A total of 7,249 cases and 72,490 controls were identified. The mean age was 48.1 years. After PSM, comorbidity incidence was higher among cases, namely dyslipidemia (18.3% vs 13.5%, p < .001), hypertension (13.8% vs 8.7%, p < .001), and obesity (8.8% vs 6.1%, p < .001). Case patients had significantly higher HRU and costs, including inpatient ($2,196 vs $1,642; p < .0016), ambulatory ($8,804 vs 4,642; p < .001), emergency room ($432 vs $350; p < .001), pharmacy ($6,878 vs $1,160; p < .001), and total healthcare costs ($18,311 vs $7,795; p < .001). LIMITATIONS: Claims data are collected for payment purposes; therefore, such data may have limitations for clinical research. CONCLUSIONS: During follow-up, DoD patients with moderate-to-severe PsO and/or PsA experienced significantly higher HRU, cost, and comorbidity burden.

Relationship between treatment persistence and A1C trends among patients with type 2 diabetes newly initiating basal insulin.

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla-100) or insulin detemir (DET) with ≥1 A1C measurement during 12-month baseline and 18-month follow-up periods were included. Patients with a refill gap of >90 days were considered non-persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow-up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non-persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Visual outcomes following optic nerve sheath fenestration via the medial transconjunctival approach.

This article determines the safety of optic nerve sheath fenestration (ONSF) for the treatment of patients with intracranial hypertension in the immediate 6-month post-operative period and its efficacy in reducing optic disk edema. Retrospective, non-comparative interventional case series. 207 eyes in 104 patients undergoing ONSF between the years 2005 and 2014. Papilledema grade based on modified Frisen scale and mean deviation of Humphrey visual field. 207 eyes of 104 patients (102 IIH, 2 IH due to dural sinus thrombosis) were included in the study. The patients were 96.1% female (N = 100) and 3.9% male (N = 4). The average patient age was 28.8 years (SD ± 9.5 years) and had a mean opening pressure of 39.85 cmH2O (SD ± 8.4 cmH2O). Mean follow-up period was 6.0 months (SD ± 5.9 months). Papilledema resolved in 76.1% of eyes at 1 week (N = 102 eyes), 75% of eyes at 1 month (N = 90 eyes), and 71% of eyes at 6 months (N = 94 eyes). Visual field comparison had a mean of the paired differences in MD at 1 week, 1 month, and 6 months of 1.59dB (P = 0.006), 2.53dB (P < 0.001), and 1.30dB (P = 0.016), respectively. ONSF is effective in reducing optic disk edema and does not cause vision loss in the 6-month post-operative period regardless of severity of IIH (as judged by elevation of opening pressure measured at pre-operative assessment).

Reduced application time for prophylactic mitomycin C in photorefractive keratectomy.

OBJECTIVE: To determine whether the duration of mitomycin C (MMC) 0.02% application affects visual outcome or the incidence of subepithelial haze in patients undergoing photorefractive keratectomy (PRK) with prophylactic administration of MMC. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Two hundred sixty-nine eyes undergoing PRK. METHODS: This was a retrospective comparative case series that included 269 eyes that underwent PRK with prophylactic MMC application for 120 seconds (group 1, n = 74), 60 seconds (group 2, n = 36), or 12 seconds (group 3, n = 159). The mean preoperative spherical equivalent was -6.49 diopters (D) in group 1, -6.77 D in group 2, and -7.10 D in group 3. Photorefractive keratectomy was performed using a modified nomogram. All eyes received a single intraoperative application of MMC (0.02%) after laser ablation for the above specified durations. MAIN OUTCOME MEASURES: Best-corrected visual acuity and corneal haze score. RESULTS: Best-corrected visual acuity was 20/23 in group 1, 20/20 in group 2, and 20/21 in group 3. The mean haze score+/-standard deviation (scale, 0.00-4.00) was 0.11+/-0.31 in group 1, 0.14+/-0.28 in group 2, and 0.07+/-0.20 in group 3 throughout a mean follow-up of 31 months in group 1, 16 months in group 2, and 10 months in group 3. No eyes had a haze score of more than 1.00. CONCLUSIONS: There was no statistically significant difference in postoperative best-corrected visual acuity or haze scores among the 3 groups. Administration of prophylactic MMC 0.02% for 12 seconds after PRK seems to be equally efficacious for haze prophylaxis when compared with longer application times of 60 and 120 seconds.