The selective oxyfunctionalization of isolated sp3 C—H bonds in complex molecules represents a formidable challenge in organic chemistry. Here, we describe a rational, systematic strategy to expedite the development of P450 oxidation catalysts with refined regio and stereoselectivity for the hydroxylation of remote, unactivated C—H sites in a complex scaffold. Using artemisinin as model substrate, we demonstrate how a three tier strategy involving first sphere active site mutagenesis, high throughput P450 fingerprinting, and fingerprint driven P450 reactivity predictions enabled the rapid evolution of three efficient biocatalysts for the selective hydroxylation of a primary and a secondary C—H site (with both S and R stereoselectivity) in a relevant yet previously inaccessible region of this complex natural product. The evolved P450 variants could be applied to provide direct access to the desired hydroxylated derivatives at preparative scales (0.4 g) and in high isolated yields (>90%), thereby enabling further elaboration of this molecule. As an example, enantiopure C7 fluorinated derivatives of the clinical antimalarial drugs artesunate and artemether, in which a major metabolically sensitive site is protected by means of a C—H to C—F substitution, were afforded via P450 mediated chemoenzymatic synthesis.

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PURPOSE: To determine patient preference and treatment outcomes with an intracanalicular dexamethasone 0.4 mg insert compared to a standard steroid drop regimen in the contralateral eye following bilateral photorefractive keratectomy (PRK). METHODS: In this randomized, prospective, self-controlled, open-label interventional study, one eye received the dexamethasone insert and the second eye received prednisolone acetate 1% taper following bilateral PRK surgery. Postoperative evaluations were performed on day 3, day 4, month 1, and month 3. Phone call surveys were performed on week 2. The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to determine patient preference between postoperative regimens and postoperative pain. Corneal endpoints included time to epithelialization, presence of corneal haze, sodium fluorescein staining, and modified Standardized Patient Evaluation of Eye Dryness (SPEED) scores. Both corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA) were assessed. RESULTS: Twenty patients participated in the study. At month 3, 70% of patients preferred the dexamethasone insert, 20% preferred prednisolone acetate, and 10% expressed no preference. Patient surveys did not show a difference in postoperative pain between the study group and control group. No statistical difference was shown in time to epithelialization, 90-day CDVA or UDVA, postoperative corneal haze, corneal staining, or modified SPEED scores. CONCLUSIONS: In patients undergoing PRK, there was preference toward a dexamethasone insert in place of topical prednisolone acetate for the postoperative steroid treatment. There were no statistically or clinically significant differences between the two cohorts in regard to healing time or visual outcomes. [ J Refract Surg . 2021;37(9):590–594.]

Introduction:In this cross-sectional study, we aimed to determine the prevalence and characteristics of chronic ocular itch in an outpatient ophthalmology and optometry clinic.Methods:Four hundred patients from an outpatient ophthalmology and optometry clinic were enrolled. The presence and characteristics of chronic ocular itch were assessed by a questionnaire. Data regarding ophthalmologic, dermatologic, and systemic conditions as well as current medications were extracted from medical records.Results:Chronic ocular itch was present in 118 (29.5%) of 400 participants. Chronic ocular pruritus was significantly more prevalent in females [P=0.015; odds ratio (OR)=1.8; 95% confidence interval (CI), 1.1–2.8] and was significantly associated with the presence of allergic conjunctivitis [51.8% (n=45); P<0.001; OR=5.0; 95% CI, 3.0–8.3], dry eye syndrome [40.1% (75); P<0.001; OR=2.6; 95% CI, 1.7–4.1], blepharitis [43.8% (n=21); P=0.021; OR=2.0; 95% CI, 1.1–3.8], and atopic dermatitis [50.0% (n=10); P=0.023; OR=2.6; 95% CI, 1.1–5.8]. Chronic ocular itch was not significantly associated with systemic conditions, or the use of prescribed ophthalmologic medications.Discussion:Chronic ocular itch is common and may be related to ophthalmologic or dermatologic pathologies. The present findings highlight the importance of identifying and managing this uncomfortable symptom that may negatively impact the quality of life and sleep of affected patients.

Purpose-To determine whether signs and symptoms of ocular surface disease improve after placement of a self-retained, cryopreserved amniotic membrane (CAM) in patients with Sjögren syndrome (SS). Methods-The medical records of SS patients who received a self-retained CAM implant (Prokera or Prokera Slim; TissueTech Inc, Doral, FL) for the treatment of ocular surface disease between August 2012 and August 2016 at a single, large academic institution were reviewed retrospectively. Visual acuity, results of slit-lamp examination of the cornea and conjunctiva, and dry eye symptoms, were evaluated before and after CAM insertion.Results-A total of 6 eyes of 6 patients (all female; mean age, 62.5 ± 13.0 years [range, 49-86 years]) were included. All patients were on topical medications at the time of the study and had signs of ocular surface dryness. There were reductions in corneal and/or conjunctival staining in 5 eyes (83%) after the CAM dissolved. All patients who completed therapy (5/5) experienced a relapse in their signs and symptoms within 1 month of removal of the CAM, with an average time to relapse of 24.6 days. Mean follow-up time was 54.5 days. Foreign body sensation and blurred vision were the most common complaints associated with the CAM implant.