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ObjectivesTo assess referral center outcomes with removal of difficult or nonpalpable contraceptive implants using high-frequency point-of-care ultrasonography.Study designWe present a case series examining patients referred to our specialty center from January 2019 through September 2020 for difficult or nonpalpable implant removal.ResultsOf the 54 referrals, 6 had palpable implants and 48 required ultrasonography. We localized 46 (96%) implants in-office, including 13 located subfascially; 2 Implanon implants could not be localized. We successfully completed 50 (96%) of 52 attempted in-office removals, including 12 (92%) subfascial implants.ConclusionHigh-frequency point-of-care ultrasonography can effectively localize nonpalpable contraceptive implants leading to successful in-office removal.ImplicationsSpecialists can use high-frequency point-of-care ultrasonography to localize nonpalpable implants without formal radiology scans and skilled technologists, optimizing patient time and convenience. However, the probe is expensive, and providers may need to consider this cost in the context of reimbursement for these highly specialized procedures.

Controlled drug delivery in the oral cavity poses challenges such as bacterial contamination, saliva dilution, and inactivation by salivary enzymes upon ingestion. Microneedles offer a location-specific, minimally invasive, and retentive approach. Hydrogel-forming microneedles (HFMs) have emerged for dental diagnostics and therapeutics. HFMs penetrate the stratum corneum, undergo swelling upon contact, secure attachment, and enable sustained transdermal or transmucosal drug delivery. Commonly employed polymers such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone are crosslinked with tartaric acid or its derivatives while incorporating therapeutic agents. Microneedle patches provide suture-free and painless drug delivery to keratinized or non-keratinized mucosa, facilitating site-specific treatment and patient compliance. This review comprehensively discusses HFMs' applications in dentistry such as local anesthesia, oral ulcer management, periodontal treatment, etc., encompassing animal experiments, clinical trials, and their fundamental impact and limitations, for example, restricted drug carrying capacity and, until now, a low number of dental clinical trial reports. The review explores the advantages and future perspectives of HFMs for oral drug delivery. [ABSTRACT FROM AUTHOR]

Among young persons, ease of use, high efficacy, and high acceptability makes the etonogestrel contraceptive implant an important choice for this age group. Adolescent-friendly, patient-centered counseling considers the patient's cognitive development, the influence of friends and family, as well as their own preferences and values. Age-appropriate language, graphics, and models are useful to explain contraceptive options and relevant side effects. Effectiveness, reversibility, safety, noncontraceptive benefits, and side effects are important attributes and should be discussed when teens are choosing a contraceptive method. In this review we describe suggested best practices for counseling adolescents about the etonogestrel implant so they can make informed, prudent decisions about using this contraceptive method.

ProblemContraceptive hormones are systemically active, potent, and likely to invoke biological responses other than known fertility regulation impacts. We hypothesized that initiation of depot medroxyprogesterone acetate (DMPA) would increase genital HIV-target-cells and soluble immune mediators compared with baseline and initiation of other contraceptive methods.Method of studyWe collected cervical cytobrushes and cervicovaginal fluid from healthy Zimbabwean women aged 18-34 to assess immune cell populations, cytokines, and innate anti-HIV activity at baseline and after 30, 90, and 180 days use of DMPA (n = 38), norethisterone enanthate (n = 41), medroxyprogesterone acetate/estradiol cypionate (n = 36), levonorgestrel implant (n = 43), etonogestrel implant (n = 47), or copper intrauterine device (Cu-IUD) (n = 45). Cells were quantified by flow cytometry, cytokines were detected by multiplex assays, and innate anti-HIV activity was assessed by in vitro HIV challenge.ResultsCompared to baseline, the number of cervical HIV target cells (#CD4 cells P

PurposeTo develop an animal model of vitreous hemorrhage (VH) to explore the impact of surgical parameters on VH associated with insertion of the Port Delivery System with ranibizumab (PDS) implant.MethodsNinety eyes from 45 treatment-naive male Yucatan minipigs received PDS implant insertion or a sham procedure. The effect of prophylactic pars plana hemostasis, scleral incision length, scleral cauterization, surgical blade type/size, and viscoelastic usage on postsurgical VH was investigated.ResultsPostsurgical VH was detected in 60.0% (54/90) of implanted eyes. A systematic effect on VH was only detected for pars plana hemostasis before the pars plana incision. The percentage of eyes with VH was 96.6% (28/29) among eyes that did not receive prophylactic pars plana hemostasis and 42.4% (24/58) among eyes that did. There was no VH in eyes that received laser ablation of the pars plana using overlapping 1,000-ms spots; pars plana cautery or diathermy was less effective. The majority of all VH cases (83.3% [45/54]) were of mild to moderate severity (involving ≤25% of the fundus).ConclusionIn this minipig surgical model of VH, scleral dissection followed by pars plana laser ablation before pars plana incision most effectively mitigated VH secondary to PDS implant insertion.

PURPOSE: To analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations. METHODS: The medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%). RESULTS: Amongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group. CONCLUSION: Latino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.

PurposeTo analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations.MethodsThe medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%).ResultsAmongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group.ConclusionLatino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from in vivo and in vitro studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect.

PrecisAt 1-year postoperative follow-up, concurrent placement of a dexamethasone intravitreal implant and glaucoma drainage device effectively controlled intraocular pressure (IOP) and inflammation in eyes with uveitic glaucoma with no changes in systemic immunomodulatory therapy.PurposeThe purpose of this study was to assess 1-year postoperative outcomes in eyes with uncontrolled uveitic glaucoma following concurrent placement of a dexamethasone intravitreal implant and glaucoma drainage device.Materials and methodsThis is a retrospective, observational case series of patients with chronic, noninfectious uveitis and uveitic glaucoma uncontrolled on maximal tolerated medical therapy with at least 1-year postoperative follow-up. The main outcomes were visual acuity, IOP, number of glaucoma medications, recurrent inflammation, frequency of topical steroids, systemic immunomodulatory therapy, and adverse events. Success was defined as IOP 20% from baseline on at least 2 consecutive visits after 3 months either with or without glaucoma medications (ie, partial or complete success, respectively).ResultsEight eyes in 6 patients met the inclusion criteria. The average age was 44.1±19.7 years (range: 10 to 68 y) and 50% were female. At 1-year, there was no significant change in visual acuity. No eyes lost ≥3 lines of vision. The majority of eyes (87.5%) achieved complete (n=2) or partial success (n=5) with a decrease in average IOP from 36.5 to 11.8 mm Hg (P=0.002). Glaucoma medication use decreased from 3.0 to 1.3 medications (P=0.04). There was a significant decrease in the number of episodes of recurrent inflammation in the 6 months following surgery compared with the 6 months before surgery (P=0.004).ConclusionIn this small case series, dexamethasone intravitreal implant combined with Ahmed glaucoma drainage device appears to be an effective approach for the management of uncontrolled uveitic glaucoma.

Study designA controlled, interventional animal study.ObjectiveSpinal implant infection (SII) is a devastating complication. The objective of this study was to evaluate the efficacy of a novel implant coating that has both a passive antibiotic elution and an active-release mechanism triggered in the presence of bacteria, using an in vivo mouse model of SII.Summary of background dataCurrent methods to minimize the frequency of SII include local antibiotic therapy (vancomycin powder), betadine irrigation, silver nanoparticles, and passive release from antibiotic-loaded poly(methyl methacrylate) cement beads, all of which have notable weaknesses. A novel implant coating has been developed to address some of these limitations but has not been tested in the environment of a SII.MethodsA biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics. The in vivo performance of this coating was tested in the delivery of either vancomycin or tigecycline in a previously established mouse model of SII. Noninvasive bioluminescence imaging was used to quantify the bacterial burden, and implant sonication was used to determine bacterial colony-forming units (CFUs) from the implant and surrounding bone and soft tissue.ResultsThe PEG-PPS-vancomycin coating significantly lowered the infection burden from postoperative day 3 onwards (P

Despite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries.

PurposeTo evaluate outcomes in patients with hypotony treated with intravitreal dexamethasone implant (Ozurdex).DesignRetrospective cohort study.ParticipantsThirteen patients (15 eyes) that received a total of 99 dexamethasone implant injections on occasions at which the intraocular pressure was low, meeting the definition of statistical hypotony.MethodsThe medical records of 13 patients (15 consecutive eyes) receiving 1 or more intravitreal dexamethasone implants between December 2014 and April 2017 were reviewed retrospectively. Hypotony was defined as intraocular pressure less than 6.5 mmHg. The indications for intravitreal dexamethasone implant injection were intermediate or posterior uveitis (86.7%), diabetic macular edema (13.3%), and/or cystoid macular edema (6.7%).Main outcome measuresThe primary outcome measures were safety outcomes and best visual acuity within 6 months of the final intravitreal dexamethasone implant injection in a hypotonous eye.ResultsIn 15 eyes (13 patients), 99 injections were administered to eyes under circumstances of hypotony. Uveitic cystoid macular edema or diabetic macular edema was reduced after treatment in all cases. No complications were noted during the injection procedure. Three complications were noted in 2 patients after injection. Pseudophakodonesis and mild vitreous hemorrhage immediately after injection were noted in 1 patient, and a case of delayed-onset vitreous hemorrhage with pigment release was noted in another. All 3 complications resolved without intervention. The primary end point of this study-mean visual acuity-was stable over the follow-up period. In patients with hypotony whose intraocular pressure normalized during the follow-up period, this was attributable to management of glaucoma surgery-related complications rather than an effect of the intravitreal dexamethasone implant.ConclusionsIntravitreal dexamethasone implant injection is a reasonable treatment option for patients with comorbid hypotony in whom clinical findings warrant treatment with a sustained-delivery intravitreal steroid implant. Further studies, including imaging of zonules before and after intravitreal dexamethasone implant injection in a hypotonous eye, could help define risks to intraocular lens stability with this procedure.

ObjectivesTo evaluate if a simple method for characterizing vaginal bleeding patterns in etonogestrel contraceptive implant users can predict subsequent patterns and bleeding-related discontinuation over the first 2 years of use.Study designWe reanalyzed phase 3 study bleeding data for non-breastfeeding participants from the United States, Europe, Russia and Chile during the first 2 years of implant use to characterize and correlate bleeding patterns. We used 90-day reference periods with period 1.1 starting at Day 29 and ending at Day 118. We dichotomized bleeding patterns as "favorable" (amenorrhea, infrequent bleeding and normal frequency bleeding without prolonged bleeding) or "unfavorable' (prolonged and/or frequent bleeding) and tracked user groups based on these bleeding patterns in reference period 1.1 through Year 1 and from Year 1 through Year 2, respectively.ResultsWe evaluated data from 537 and 428 women with up to 1 and 2 years use, respectively. Of the 325 (60.5%) women with favorable bleeding in reference period 1.1, 275 (84.6%) reported favorable bleeding also in reference period 2, 197 (60.6%) reported favorable bleeding throughout Year 1, and favorable bleeding in 75-85% of reference periods in Year 2. Among 212 (39.5%) women with unfavorable bleeding in reference period 1.1, 118 (55.7%) continued with unfavorable bleeding in reference period 2, while about 40%-50% reported favorable patterns in RP 2, 3 and/or 4. Initial favorable bleeding resulted in lower discontinuation rates than initial unfavorable bleeding in years 1 (3.7% vs 12.7%, p≪.0001) and 2 (2.5% vs 16.5%, p≪.0001).ConclusionImplant users with favorable bleeding in the first reference period are likely to continue with favorable bleeding over the next 2 years. Initial bleeding patterns predict overall continuation rates in years 1 and 2. Implications Statement When evaluating vaginal bleeding in any 90-day reference period over 2 years of etonogestrel implant use, approximately 80% of women with favorable and 40% with unfavorable bleeding patterns will have favorable bleeding in the next reference periods. These findings can facilitate counseling regarding bleeding for women using the etonogestrel implant.

There is a limit beyond which increasing either the concentration of a prostaglandin analog (PGA) or its dosing frequency fails to produce increases in ocular hypotensive efficacy with topical dosing. Intracameral PGA dosing with a bimatoprost implant, however, does not exhibit the same intraocular pressure (IOP)-lowering plateau at studied concentrations, and the maximum-achievable ocular hypotensive effects are not yet known. This suggests that the bimatoprost intracameral implant may activate another mechanism of action in addition to the mechanism(s) activated by topical application. Episcleral venous pressure (EVP) is a key determinant of IOP, and experimental manipulation of the episcleral vasculature can change both EVP and IOP. The recent observation that topical and intracameral PGA drug delivery routes produce different patterns of conjunctival hyperemia suggested that the differences in the IOP-lowering profiles may be caused by differing effects on the episcleral vasculature. Recent experiments in animals have shown that topical PGAs increase EVP, while the bimatoprost intracameral implant causes a smaller, transient increase in EVP, followed by a sustained decrease. The increase in EVP could be limiting the IOP-lowering efficacy of topical PGAs. In contrast, the decrease in EVP associated with the bimatoprost implant could explain its enhanced IOP-lowering effects. Further research on EVP as a target for IOP lowering is indicated to improve our understanding of this potentially important pathway for treating patients with glaucoma.

Topical eye-drop administration and intravitreal injections are the current standard for ocular drug delivery. However, patient adherence to the drug regimen and insufficient administration frequency are well-documented challenges to this field. In this review, we describe recent advances in intraocular implants designed to deliver therapeutics for months to years, to obviate the issues of patient adherence. We highlight recent advances in monolithic ocular implants in the literature, the commercialization pipeline, and approved for the market. We also describe design considerations based on material selection, active pharmaceutical ingredient, and implantation site.

OBJECTIVE:Cisplatin is a chemotherapeutic drug known to induce hearing loss. Although corticosteroids may help to mitigate the ototoxic side effects of cisplatin, there are complications associated with their systemic and prolonged use. The goal of this study is to test the efficacy of extended-release fluticasone propionate intracochlear implant particles to protect against cisplatin-induced hearing loss. METHODS:We used guinea pigs (n = 9) injected with cisplatin (IP, 12 mg/kg weight). Fluticasone particles were delivered to the cochlear scala tympani through the round window membrane into the right ears of the guinea pigs (left ears being used as a control) two weeks prior to cisplatin administration, and hearing function was evaluated by ABR and DPOAE before implantation, immediately before cisplatin administration, and 2 weeks after the challenge with cisplatin. Data was statistically evaluated using paired t-test analysis. RESULTS:No significant differences were observed in ABR threshold between control and implanted ears on day 14 (23.9 ± 2.3 dB vs. 25.6 ± 1.3 dB, P = 0.524), whereas the significant cisplatin-induced hearing loss in control animals (23.9 ± 2.3 dB at day 14 vs. 40.7 ± 2.5 dB at day 28, P ≤ 0.0001) was prevented in implanted animals (25.6 ± 1.3 dB at day 14 vs. 25.0 ± 3.1 at day 28, P ≥ 0.85). A similar, though not statistically significant, trend was observed in DPOAE responses in untreated ears (7.9 ± 5.8 dB at day14 vs. -0.5 ± 5.3 dB at day 28, P = 0.654) as compared to treatment (11.1 ± 3.4 dB at day 14 vs. 13.6 ± 4.8 dB at day 28, P = 0.733). CONCLUSION:These results suggest that fluticasone intracochlear implants are safe and able to provide effective otoprotection against cisplatin-induced hearing loss in the guinea pig model.

PurposeTo test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy.DesignRandomized sham-controlled clinical trial.ParticipantsNinety-nine study eyes of 67 eligible participants were enrolled.MethodsSingle-masked randomized clinical trial of 24 months' duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure.Main outcome measuresThe primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups.ResultsAmong the 67 participants who were randomized (mean age, 62±8.9 years; 41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05±0.03 mm2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than that of the treated group (decrease, 15.81±8.93 dB; P = 0.07). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (4%) in the treated group.ConclusionsIn participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety.

PurposeTo evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI).DesignMulticenter, randomized clinical trial.ParticipantsPatients with uveitic ME.MethodsPatients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes.Main outcome measuresThe primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included ≥20% improvement and resolution of ME, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks.ResultsAll treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, hazard ratio [HR], 0.79; 99.87% confidence interval [CI], 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87% CI, 0.56-0.86) had larger reductions in CST than PTA (P < 0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, HR, 0.88; 99.87% CI, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in the PTA group at 8 weeks (P < 0.004). The risk of having IOP ≥24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (HR, 1.83; 95% CI, 0.91-3.65 and HR, 2.52; 95% CI, 1.29-4.91 for ITA and IDI, respectively); however, there was no significant difference between the 2 intravitreal treatment groups.ConclusionsIntravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic ME with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments.

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ObjectiveCalcium hydroxyapatite (CaHA) is a common material for vocal fold injection augmentation. Durability is variable, and factors involved in implant longevity are not understood. Animal models of osteoporosis show decreased bone density and increased mineral liberation, suggesting CaHA retention may be altered in these conditions.Study designProspective murine investigation.MethodsFourteen skeletally mature, 10-month-old female Sprague-Dewley rats were treated by one of three interventions: oophorectomy, laparotomy without oophorectomy (sham), or monthly risedronate injection (90 μg/kg, subcutaneous). CaHA was implanted into the right lateral thigh muscle in all animals at the time of procedure or first risedronate injection. After 17 weeks, all rats were sacrificed, and the residual CaHA isolated from excised lateral thigh muscle through incubation in a 900 °C calcinator for 9 hours.ResultsMean CaHA mass remaining in the oophorectomy group was 65.9 (standard deviation ± 16.1) mg, compared to 44.4 ± 10.0 mg CaHA in the risedronate group and 48.6 ± 7.5 mg in the sham group. One-way analysis of variance found a statistically significant difference between the oophorectomy and risedronate groups but not between the sham and other groups, F(2,11) = 4.404, P = 0.039.ConclusionPersistent estrogen deficiency in a murine model of osteoporosis demonstrated decreased rate of CaHA resorption. This suggests that hormone alterations associated with osteoporosis may alter the longevity of CaHA implant resorption through an uncertain mechanism.Level of evidenceNA. Laryngoscope, 2576-2580, 2018.

BackgroundUS unintended pregnancy rates remain high, and contraceptive providers are not universally trained to offer intrauterine devices and implants to women who wish to use these methods.ObjectiveWe sought to measure the impact of a provider training intervention on integration of intrauterine devices and implants into contraceptive care.Study designWe measured the impact of a continuing medical education-accredited provider training intervention on provider attitudes, knowledge, and practices in a cluster randomized trial in 40 US health centers from 2011 through 2013. Twenty clinics were randomly assigned to the intervention arm; 20 offered routine care. Clinic staff participated in baseline and 1-year surveys assessing intrauterine device and implant knowledge, attitudes, and practices. We used a difference-in-differences approach to compare changes that occurred in the intervention sites to changes in the control sites 1 year later. Prespecified outcome measures included: knowledge of patient eligibility for intrauterine devices and implants; attitudes about method safety; and counseling practices. We used multivariable regression with generalized estimating equations to account for clustering by clinic to examine intervention effects on provider outcomes 1 year later.ResultsOverall, we surveyed 576 clinic staff (314 intervention, 262 control) at baseline and/or 1-year follow-up. The change in proportion of providers who believed that the intrauterine device was safe was greater in intervention (60% at baseline to 76% at follow-up) than control sites (66% at both times) (adjusted odds ratio, 2.48; 95% confidence interval, 1.13-5.4). Likewise, for the implant, the proportion increased from 57-77% in intervention, compared to 61-65% in control sites (adjusted odds ratio, 2.57; 95% confidence interval, 1.44-4.59). The proportion of providers who believed they were experienced to counsel on intrauterine devices also increased in intervention (53-67%) and remained the same in control sites (60%) (adjusted odds ratio, 1.89; 95% confidence interval, 1.04-3.44), and for the implant increased more in intervention (41-62%) compared to control sites (48-50%) (adjusted odds ratio, 2.30; 95% confidence interval, 1.28-4.12). Knowledge scores of patient eligibility for intrauterine devices increased at intervention sites (from 0.77-0.86) 6% more over time compared to control sites (from 0.78-0.80) (adjusted coefficient, 0.058; 95% confidence interval, 0.003-0.113). Knowledge scores of eligibility for intrauterine device and implant use with common medical conditions increased 15% more in intervention (0.65-0.79) compared to control sites (0.67-0.66) (adjusted coefficient, 0.15; 95% confidence interval, 0.09-0.21). Routine discussion of intrauterine devices and implants by providers in intervention sites increased significantly, 71-87%, compared to in control sites, 76-82% (adjusted odds ratio, 1.97; 95% confidence interval, 1.02-3.80).ConclusionProfessional guidelines encourage intrauterine device and implant competency for all contraceptive care providers. Integrating these methods into routine care is important for access. This replicable training intervention translating evidence into care had a sustained impact on provider attitudes, knowledge, and counseling practices, demonstrating significant changes in clinical care a full year after the training intervention.

BackgroundData evaluating the impact of contraceptives on the vaginal microbiome are limited and inconsistent.ObjectiveWe hypothesized that women initiating copper intrauterine device use would have increased bacterial vaginosis and bacterial vaginosis-associated microbes with use compared to women initiating and using hormonal contraceptive methods.Study designVaginal swabs (N = 1047 from 266 participants seeking contraception) for Nugent score determination of bacterial vaginosis and quantitative polymerase chain reaction analyses for assessment of specific microbiota were collected from asymptomatic, healthy women aged 18-35 years in Harare, Zimbabwe, who were confirmed to be free of nonstudy hormones by mass spectrometry at each visit. Contraception was initiated with an injectable (depot medroxyprogesterone acetate [n = 41], norethisterone enanthate [n = 44], or medroxyprogesterone acetate and ethinyl estradiol [n = 40]), implant (levonorgestrel [n = 45] or etonogestrel [n = 48]), or copper intrauterine device (n = 48) and repeat vaginal swabs were collected after 30, 90, and 180 days of continuous use. Self-reported condom use was similar across all arms at baseline. Quantitative polymerase chain reaction was used to detect Lactobacillus crispatus, L jensenii, L gasseri/johnsonii group, L vaginalis, L iners, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera-like bacterium phylotype I from swabs. Modified Poisson regression and mixed effects linear models were used to compare marginal prevalence and mean difference in quantity (expressed as gene copies/swab) prior to and during contraceptive use.ResultsBacterial vaginosis prevalence increased in women initiating copper intrauterine devices from 27% at baseline, 35% at 30 days, 40% at 90 days, and 49% at 180 days (P = .005 compared to marginal prevalence at enrollment). Women initiating hormonal methods had no change in bacterial vaginosis prevalence over 180 days. The mean increase in Nugent score was 1.2 (95% confidence interval, 0.5-2.0; P = .001) in women using copper intrauterine devices. Although the frequency and density of beneficial lactobacilli did not change among intrauterine device users over 6 months, there was an increase in the log concentration of G vaginalis (4.7, 5.2, 5.8, 5.9; P = .046) and A vaginae (3.0, 3.8, 4.6, 5.1; P = .002) between baseline and 30, 90, and 180 days after initiation. Among other contraceptive groups, women using depot medroxyprogesterone acetate had decreased L iners (mean decrease log concentration = 0.8; 95% confidence interval, 0.3-1.5; P = .004) and there were no significant changes in beneficial Lactobacillus species over 180 days regardless of contraceptive method used.ConclusionCopper intrauterine device use may increase colonization by bacterial vaginosis-associated microbiota, resulting in increased prevalence of bacterial vaginosis. Use of most hormonal contraception does not alter vaginal microbiota.

OBJECTIVE:We evaluated a novel concept of initiating the etonogestrel implant as a "back-up" method in women who desire using combined oral contraceptives (COC) but want to decrease their risk of unintended pregnancy with a more effective method. STUDY DESIGN:In this prospective cohort study, we planned to include 20 women as a proof-of-concept. We enrolled both new COC starters and continuing COC users and placed an etonogestrel implant. Participants completed daily bleeding diaries and attended follow-up visits at 1, 3, and 6 months. We assessed implant continuation through six months of study participation and side effects with dual hormonal contraceptive use. RESULTS:Between September and December 2016, we enrolled 10 new starters and 10 current COC users. All participants completed 1-month follow-up, and 18 (90%) subjects completed the 3- and 6-month follow-up assessments. Two current COC users had the implant removed for mood changes before 6 months. At the 6-month follow-up visit, 10 women were using both pills and implant, seven relied on the implant only, and one was using a COC only. Three new starters chose implant removal at end of study participation; one for weight gain and acne, another for mood changes, and one for decreased libido. No subjects discontinued the implant for bleeding complaints. CONCLUSION:In this proof-of-concept study, women using COCs were willing to initiate the implant as a "back-up" method to improve pregnancy prevention. Most women continued the implant through 6 months and after completing study participation. IMPLICATIONS:Initiating the etonogestrel implant as a "back-up" method may be an option for women who desire more effective pregnancy prevention while using combined oral contraceptive pills for its bleeding profile or non-contraceptive benefits.

Implantation of biodegradable wafers impregnated with carmustine (BCNU) is one of the few chemotherapeutic modalities that have been evaluated in Phase III trials and approved by the US FDA for treatment of newly diagnosed high-grade glioma and recurrent glioblastoma. Enrolling up to 500 patients for 3-year follow-up at over 30 sites, the prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT (VIGILANT) registry (NCT02684838) will evaluate BCNU wafers for treatment of CNS malignancies in contemporary practice and in the new era of molecular tumor analysis. Subgroup analyses will include tumor type, molecular marker status, and treatment combinations. Interim analyses from the VIGILANT registry will be reported until complete results are available in 2024.

Electrospun fibers have been gaining popularity in ocular drug delivery and cellular therapies. However, most of electrospun fibers are planar-shape membrane with large dimension relative to intraocular space, making difficult to use as therapeutic implants. Herein, fibrous microtubes with a hollow center were fabricated by electrospinning using linear diblock mPEG 2000 -PLGA. Uniform microfibers with 0.809 μm diameter was tailored using Box-Behnken Design model for electrospinning process optimization. The microtubes were 1 mm long with a 0.386 mm diameter. Their suitability for intraocular administration was demonstrated by both injection via a 22-gauge needle and implant via integration of intraocular lens into the vitreous or anterior chamber of eyes, respectively. Electrospun mPEG 2000 -PLGA had higher porosity, smaller specific surface area, and smaller water contact angle, than that of PLGA. Macroscopically, mPEG 2000 -PLGA microfibers can maintain overall geometry upon exposure to aqueous buffer for 12 h while having high water uptake and exhibited good elasticity. Hydrolysis with 90 % polymeric degradation in 10.5 weeks underlied sustained slow release of anti-inflammatory drug dexamethasone. PEGylation of PLGA imparted preferential cell adhesion with markedly higher growth of human retinal epithelial cells than lens epithelial ones. This study highlights the potential utility of implantable electrospun PLGA-based microtubes for multiple intraocular delivery routes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Drug delivery routes play an essential role in determining the efficacy and safety of medications. This study focused on the development and optimization of 3D-printed reservoir type implants as a combinational therapy drug delivery system for Glioblastoma Multiforme (GBM) post-surgery, possessing also antibacterial properties. In this study, we used a multimodal agent, Acriflavine (ACF) as an alternative drug to treat GBM. To date, ACF is used only as an antiseptic agent, although it has been shown to possess strong anticancer activities. ACF and a low molecular weight PCL were loaded into 3D-printed reservoir-type implants for sustained drug delivery. The study demonstrated that ACF implants exhibited sustained drug release kinetics, with faster release during the initial 30 days, followed by a gradual decrease over 90 days. This controlled release profile enhances the effectiveness of ACF delivery to tumour targets while minimizing side effects associated with systemic administration. In vitro experiments confirmed the inhibitory activity of ACF against GBM cells compared to non-tumour cells. The study also highlighted the bacteriostatic effects of ACF, making the implants potentially useful for post-surgery infection management, particularly against S. aureus, a common bacterial infection associated with brain surgery. The long-term drug-release capabilities of the implants make them attractive candidates for both tumour inhibition and antibacterial treatment. The study suggests that the developed ACF delivery systems have the potential for future clinical studies. Their ability to provide increased drug efficacy without systemic toxicity makes them promising candidates for cancer therapy and post-surgery infection management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Schizophrenia is a severe mental disorder that affects millions of people worldwide. Several atypical antipsychotic medications, including paliperidone (PPD), has been developed and proven effective in treating it. To date, four PPD extended-release products have been launched commercially, providing up to six months of therapeutic effect with a single administration. However, the need for hospital injections by professional healthcare workers not only lead to poor patients' adherence, but also put additional pressure on the healthcare system. Therefore, three PPD microarray patch (PPD MAP) systems based on dissolving microneedle technology and implantable microneedle technology were developed in this work. The two dissolving microarray patch systems contained either PPD crude drug (PPD DMAP-CD) or PPD nanocrystal (PPD DMAP-NC) and the implantable MAP contained PPD crude drug (PPD IMAP). All three types of PPD MAPs showed excellent mechanical and insertion properties as they achieved over 256 µm insertion depth in skin model. In vitro release study showed that PPD released from IMAP in a much more sustained manner (up to 14 days) than PPD did from DMAPs (7 days), with only 20 % initial burst release from IMAP compared with 43-71 % from DMAPs. The MAP dissolution study showed that both DMAPs can be immediately dissolved within less than 3 min once inserted into the skin, indicating a faster action potential compared with IMAP. Ex vivo delivery study showed that 1.68 ± 0.23 mg, 1.39 ± 0.07 mg, and 1.18 ± 0.12 mg were delivered from DMAP-CD, DMAP-NC and IMAP, respectively, demonstrating that over 50 % and up to 70 % of PPD in the MAPs can be delivered into the skin. The IMAP offers most sustained release of PPD whereas DMAP-NC exhibits fastest PPD release (11.19 % vs 20.01 % into Franz cell receiver compartment over 24 h). This work presents a promising alternative for the sustained delivery of antipsychotic drugs, allowing for patient self-administration and extended release concurrently. Patients may potentially use both DMAP and IMAP to achieve a sustained release of PPD while also avoid having an initial therapeutic lag., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Ryan Donnelly is an inventor of patents that have been licensed to companies developing microneedle-based products and is a paid advisor to companies developing microneedle-based products. The resulting potential conflict of interest has been disclosed and is managed by Queen’s University Belfast. The companies had no role in any part of this study.]., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To assess macular thickness fluctuations and their association with visual acuity outcomes in eyes with diabetic macular edema treated with an intravitreal dexamethasone (DEX) implant., Methods: The SD of all postbaseline central subfield thicknesses (CST) recorded over a 12-month period after the first injection of the DEX implant was used to quantify CST fluctuations. Linear regression models were used to identify factors associated with the visual acuity at 12 months (measured with the Early Treatment of Diabetic Retinopathy Study score) and predictors of CST SD., Results: A retrospective review of 80 eyes of 80 patients treated with the DEX implant for diabetic macular edema revealed a CST SD of 75.3 ± 50.3 µ m. The CST SD was negatively associated with the visual acuity at 12 months (-7.7 Early Treatment of Diabetic Retinopathy Study letters for each 100- µ m increase in CST SD, P = 0.01), while changes in CST from baseline did not show any significant association. Eyes were stratified into quartiles based on the CST SD, and a difference by -14.2 letters in visual acuity at 12 months was observed between the first and fourth quartiles ( P <0.001). Significant predictors of CST SD included the baseline visual acuity (-12.0 µ m for each 10-letter increase, P = 0.02) and the number of DEX injections received (n = 17.1, P = 0.03)., Conclusion: Greater fluctuations in retinal thickness were found to be associated with poorer visual outcomes in eyes with diabetic macular edema treated with the DEX implant. Analyzing the CST SD could be a more predictive indicator of visual prognosis than individual measurements of the CST.

Purpose: The 0.18 mg fluocinolone acetonide implant (FAi) is marketed for up to 36 months for treatment of noninfectious uveitis. An additional short-term corticosteroid burst prior to the 0.18 mg FAi, followed by attempt at long-term inflammation control with the 0.18 mg FAi may be beneficial given the low dose of the implant. We retrospectively reviewed all patients undergoing this treatment approach at our institution to determine its efficacy., Methods: Patients who received a corticosteroid burst followed by the 0.18 mg FAi with at least 6-month follow-up post 0.18 mg FAi were included. The primary outcome, treatment escalation (defined as worsening inflammation requiring escalation of therapy), was modeled using Kaplan-Meier analysis. Secondary outcomes included cystoid macular edema (CME), central macular thickness, retinal vasculitis, visual acuity, anterior chamber and vitreous cell, use of systemic therapy, use of corticosteroid drops, IOP, number of IOP lowering medications, need for glaucoma surgery, need for cataract surgery, and additional local corticosteroids., Results: 32 eyes were included (mean follow-up: 19.8 months). Prior to corticosteroid burst, 37.5% were on systemic therapy, 53% had CME, and 25% had retinal vasculitis. At FAi visit, CME had decreased to 18.8%. Mean time to treatment escalation after FAi was 20.3 months (95% CI 14.8-25.7 months). No patient discontinued systemic therapy and on average 15.0% of eyes required additional local corticosteroids at each follow-up interval., Conclusions: This treatment approach demonstrates that the 0.18 mg FAi is a useful adjuvant for the treatment of noninfectious uveitis but may not be adequate as solo therapy.

Background: Little is known about the degree to which the COVID-19 pandemic, and associated restrictions and disruptions to health services, impacted the accessibility of hormonal long-acting reversible contraception (LARC) devices within Australia. Here, we explore longitudinal patterns of dispensing of the contraceptive implant and hormonal intrauterine devices (IUDs) within Australia, before and during the COVID-19 pandemic., Methods: Population-based cohort study; analysis of 10% random sample of national Pharmaceutical Benefits Scheme dispensing data, for females aged 15-49 years dispensed a hormonal LARC device between February 2017 and November 2021., Results: Interrupted time-series analysis demonstrated overall that there were no significant differences in monthly dispensing rates of hormonal LARC following the Australian onset of the pandemic in April 2020, with no subsequent change in the trend. However, when stratified by LARC type, a significant increase was evident during the pandemic period (April 2020-November 2021) in the rate of hormonal IUD dispensing per month (0.20 per 10 000 95% CI 0.01 to 0.38)), compared with a decrease for the implant (-0.08 per 10 000 (95% CI -0.16 to 0.01)). Increases in hormonal IUD dispensing during the pandemic were most pronounced for those aged 20-24 years, new users, those without a Commonwealth concession card, and in the State of Victoria., Conclusions: Within Australia in the defined pandemic period, access to hormonal LARC devices was not negatively impacted. Rather a significant increase in dispensing of hormonal IUDs was evident., Competing Interests: Competing interests: DB and DM have received honoraria, and research and travel funding from pharmaceutical companies marketing long-acting reversible contraception (LARC) products including Bayer and Organon., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the frequency of early discontinuation of Implanon as a method of contraception., Methods: The cohort prospective study was conducted at the Obstetrics and Gynaecology Department, Al-Yarmouk Teaching Hospital, Baghdad, Iraq from January 2017 to January 2021, after approval from the ethics review committee of the College of Medicine, Al-Mustansiriyha University, Bghadad, Iraq, and comprised women of childbearing age seeking long-acting contraception. The participants received Implanon, an etonorgestril implant, under local anaesthesia, and were followed up for 12 months for possible side effects. Data was analysed using SPSS 26., Results: There were 115 women with mean age 29.8±6 years (range: 15-44 years) and mean body mass index 27±4.9 kg/m2. Early discontinuation of the plant was done by 32(27.8%) subjects, and the overall incidence of early Implanon removal per 1,000 women per month was 14.47 (95% confidence interval: 10.24-20.47). Lower body mass index, dizziness and insertion-site side effects were the potential determinants of early discontinuation (p<0.05)., Conclusions: More than a quarter of the sample opted for early Implanon discontinuation. Low body mass index, dizziness and insertion-site side effects were potential determinants of early removal.

Purpose: This study reports the outcomes of the 0.18-mg intravitreal fluocinolone acetonide implant in the treatment of pediatric noninfectious uveitis., Methods: A retrospective cohort study was performed on patients under 18 years old who received fluocinolone acetonide implant between June 1, 2020 and March 1, 2023. Data collected included demographics, uveitis diagnosis, use of anti-inflammatory therapy, visual acuity, intraocular pressure, and grading of uveitis activity. Uveitis recurrence was defined as increased inflammation that required additional anti-inflammatory therapy., Results: Eleven eyes from seven patients were included in this study. One patient (one eye) had a diagnosis of immune recovery uveitis and the remaining six patients (10 eyes) had pars planitis. The rate of remaining recurrence-free was 82% at 6 months, 60% at 12 months, and 60% at 24 months. Two of the six phakic eyes at baseline required cataract extraction during follow-up. Two of the four eyes that did not have intraocular pressure-lowering surgery before implantation required surgery in follow-up., Conclusion: The 0.18-mg fluocinolone acetonide implant has a similar efficacy for the treatment of pediatric uveitis, particularly pars planitis, as in the adult population, although with higher rates of ocular hypertension requiring intervention.

Aim: The purpose of this study was to conduct and interpret a pooled 12-month analysis of two prospective, multi-center, randomized, double-masked, controlled trials designed to assess the efficacy and safety of the travoprost intracameral implant (slow-eluting [SE] implant in development as a new therapeutic and fast-eluting [FE] implant included for masking purposes) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT)., Methods: Subjects with OAG or OHT, on 0-3 intraocular pressure (IOP)-lowering medications, baseline unmedicated mean diurnal IOP of ≥ 21 mmHg, and IOP ≤ 36 mmHg at each baseline diurnal timepoint, received either a travoprost implant and twice-daily (BID) placebo eye drops or BID timolol 0.5% eye drops and a sham procedure. Subjects were followed through 12 months and assessed for IOP, reduction in topical IOP-lowering medications, and safety parameters including treatment-emergent adverse events (TEAEs). IOP at 8AM was prospectively collected at all study visits through 12 months and diurnal IOP, measured at 8AM, 10AM, and 4PM, was prospectively collected at baseline, day 10, week 6, and months 3 and 12., Results: A total of 1150 subjects were randomized (385 FE implant, 380 SE implant, and 385 sham/timolol) across the two trials. Statistical non-inferiority to timolol and clinically relevant reductions in 8AM IOPs were demonstrated at month 12. In more detail, both implant groups demonstrated statistical non-inferiority to timolol and clinically relevant reductions from baseline in mean diurnal IOP at all visits over the 12-month evaluation period when diurnal IOP was collected. Additionally, both implant groups demonstrated robust treatment effect based on 8AM average IOP from day 10 through the specified visit which ranged from day 10 to month 12 from 6.9 to 8.5 mmHg in the FE implant group; 6.8 to 8.5 mmHg in the SE implant group; and 7.3 to 7.5 mmHg in the sham/timolol group. With regards to reduction in topical pharmacotherapy, at month 12, 77.6% of FE and 81.4% of SE implant eyes were completely free of all topical IOP-lowering medications and a significantly greater proportion of FE and SE implant eyes (89.9% and 93.0%) versus sham/timolol eyes (66.9%) were on the same or fewer topical IOP-lowering medications compared with pre-study (p <  0.0001). Furthermore, of subjects on topical IOP medications at screening, a significantly greater proportion of FE implant (80.2%) and SE implant (85.1%) eyes versus sham/timolol (22.8%) eyes were on fewer topical IOP-lowering medications at month 12 compared with pre-study (p <  0.0001). Lastly, of SE implant eyes on same or fewer topical IOP-lowering medications at month 12, the average through month 12 decreased by 0.9 medications, and of those SE implant eyes on fewer topical IOP-lowering medications compared with pre-study, the average through month 12 decreased by 1.4 medications. The most common TEAEs related to study treatment were hyperemia (conjunctival or ocular), iritis, and IOP increased., Conclusion: The travoprost intracameral implant demonstrated robust IOP-lowering efficacy that was sustained and statistically non-inferior to timolol over the entire 12 months, resulting in a significant reduction in topical IOP-lowering medication use, with the majority of SE implant eyes remaining completely free of all topical IOP-lowering medications. In addition, the implant demonstrated a favorable safety and tolerability profile based on this pooled 12-month analysis of two pivotal trials., Trial Registration: ClinicalTrials.gov identifiers NCT03519386 (registered May 09, 2018) and NCT03868124 (registered March 08, 2019)., (© 2024. The Author(s).)

Objective: To evaluate body mass index (BMI) over 36 months among adolescents and young adults using the etonogestrel implant compared with those using depot medroxyprogesterone acetate (DMPA) and a control group., Methods: We conducted a retrospective longitudinal cohort study of postmenarchal adolescents and young adults assigned female at birth. The etonogestrel implant and DMPA groups initiated etonogestrel or DMPA between January 1, 2010, and December 31, 2017. Adolescents and young adults in the control group were prescribed a weight-neutral contraceptive or no contraceptive during the same timeframe. The primary outcome of BMI over time was estimated and compared between study groups with inverse probability of treatment weighting linear mixed-effects modeling. Changes in BMI weight category (underweight or normal weight, overweight, obesity) at 12, 24, and 36 months were also explored., Results: Among the 20,409 eligible patients, 860 initiated etonogestrel, 1,817 initiated DMPA, and 17,732 made up the control group. Compared with individuals in the control group, those in the etonogestrel group had a significantly higher mean BMI difference at 9 months (+0.5, P <.01); at 36 months, the mean BMI difference was +1.0 ( P <.01). Compared with individuals in the control group, those in the DMPA group had higher mean BMI at 6 months (+0.3, P <.01); at 36 months, the mean BMI difference was +1.3 ( P <.01). Regardless of weight changes, increases in BMI weight categories were rare in all groups., Conclusion: Adolescent and young adult patients who initiated the etonogestrel implant demonstrated BMI changes like those on DMPA and higher than control patients; however, these differences may not be clinically concerning. This study provides important information that can help in counseling adolescent and young adult patients about expectations when starting and using etonogestrel., Competing Interests: Financial Disclosure Elise Berlan reports research funding from Merck and Organon, and she is a Nexplanon Clinical Trainer for Merck and Organon. Her institution also received funding from Organon. She has been a Section Editor and peer reviewer for UpToDate. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intraocular dexamethasone implant (DEXi) is an efficient treatment for diabetic macular edema (DME). However, it may be unavailable or contraindicated. Triamcinolone acetonide is another corticosteroid that has proved to be safe and effective in treating macular edema complicating various diseases including diabetes. The purpose of this study is to evaluate the outcomes of a switch from DEXi to subtenon triamcinolone acetonide (STTA) and back, in eyes with DME., Methods: Retrospective study. DME eyes that had been treated with DEXi and switched to STTA between October 2018 and February 2019 (stock shortage of DEXi) were included. The functional and anatomical outcomes of the switch and switch-back were studied., Results: 26 eyes of 17 patients (mean age 67.1 ± 8.2 years) were considered. The mean baseline visual acuity (VA) was 0.35 ± 0.17 decimals remaining stable after DEXi, STTA and switch-back to DEXi. The mean central macular thickness (CMT) was 492.7 ± 32.8 µm initially, decreasing to 294.3 ± 133.4 µm after DEXi, 369.9 ± 182.3 µm after STTA and 297.6 ± 72.0 µm after switching back to DEXi (all p < 0.05 versus baseline). Compared to baseline, the CMT reduction was numerically better after DEXi and switching back to DEXi than after STTA (mean reduction: -200.4 µm, -167.7 µm, and -95.08 µm respectively, p = 0.13). Intraocular pressure was comparable after DEXi and STTA., Conclusion: DEXi is the steroid of choice in DME. However, STTA can be a cost-effective alternative when DEXi is unavailable or contraindicated. This study suggests that STTA may be used in the context of a step therapy in DME., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options., Objective: To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH., Design, Setting, and Participants: This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria. Consecutive patients with World Federation of Neurological Surgeons grade 3 or 4 aSAH due to a ruptured anterior circulation aneurysm requiring microsurgical aneurysm repair participated., Intervention: During aneurysm repair, patients were randomized 1:1 to intraoperatively receive 10 implants at 4 mg of nicardipine each plus standard of care (implant group) or aneurysm repair alone plus standard of care (control group)., Main Outcome and Measures: The primary end point was the incidence of moderate to severe cerebral angiographic vasospasm (aVS) between days 7 and 9 after aneurysm rupture as determined by digital subtraction angiography., Results: Of 41 patients, 20 were randomized to the control group (mean [SD] age, 54.9 [9.1] years; 17 female [85%]) and 21 to the implant group (mean [SD] age, 53.6 [11.9] years; 14 female [67%]). A total of 39 patients were included in the primary efficacy analysis. In the control group, 11 of 19 patients (58%) developed moderate or severe aVS compared with 4 of 20 patients (20%) in the implant group (P = .02). This outcome was paralleled by a lower clinical need for vasospasm rescue therapy in the implant group (2 of 20 patients [10%]) compared with the control group (11 of 19 patients [58%]; P = .002). Between days 13 and 15 after aneurysm rupture, new cerebral infarcts were noted in 6 of 19 patients (32%) in the control group and in 2 of 20 patients (10%) in the implant group (P = .13). At 52 weeks, favorable outcomes were noted in 12 of 18 patients (67%) in the control group and 16 of 19 patients (84%) in the implant group (P = .27). The adverse event rate did not differ between groups., Conclusions and Relevance: These findings show that placing nicardipine release implants during microsurgical aneurysm repair can provide safe and effective prevention of moderate to severe aVS after aSAH. A phase 3 clinical trial to investigate the effect of nicardipine implants on clinical outcome may be warranted., Trial Registration: ClinicalTrials.gov Identifier: NCT04269408.

HIV prevention with pre-exposure prophylaxis (PrEP) constitutes a major pillar in fighting the ongoing epidemic. While daily oral PrEP adherence may be challenging, long-acting (LA-)PrEP in oral or implant formulations could overcome frequent dosing with convenient administration. The novel drug islatravir (ISL) may be suitable for LA-PrEP, but dose-dependent reductions in CD 4 + T cell and lymphocyte counts were observed at high doses. We developed a mathematical model to predict ISL pro-drug levels in plasma and active intracellular ISL-triphosphate concentrations after oral vs. subcutaneous implant dosing. Using phase II trial data, we simulated antiviral effects and estimated HIV risk reduction for multiple dosages and dosing frequencies. We then established exposure thresholds where no adverse effects on immune cells were observed. Our findings suggest that implants with 56-62 mg ISL offer effective HIV risk reduction without reducing lymphocyte counts. Oral 0.1 mg daily, 3-5 mg weekly, and 10 mg biweekly ISL provide comparable efficacy, but weekly and biweekly doses may affect lymphocyte counts, while daily dosing regimen offered no advantage over existing oral PrEP. Oral 0.5-1 mg on demand provided > 90 % protection, while not being suitable for post-exposure prophylaxis. These findings suggest ISL could be considered for further development as a promising and safe agent for implantable PrEP., (© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose: To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab., Methods: This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up., Results: In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007)., Conclusions: In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.

Objective: This study seeks to explain the relationship between systemic conditions and hard exudate formations in diabetic macular edema patients. Besides, the study aimed to quantitatively examine changes in the area, location, and impact on visual function of hard exudates following intravitreal dexamethasone implant injections., Methods: A retrospective analysis was conducted, including 40 patients (40 eyes) diagnosed with non-proliferative diabetic retinopathy and concurrent macular edema between January 1, 2022, and January 1, 2024. Preoperative evaluations included glycated hemoglobin, lipid profile, and renal function examinations. Based on the location of HE, patients were divided into two groups: Group A, with HE in 1 mm of the central fovea, and Group B, with HE outside 1 mm of the central fovea. Selected eyes were subject to pre- and postoperative examinations, including best-corrected visual acuity (BCVA), intraocular pressure, slit-lamp biomicroscopy, scanning laser ophthalmoscopy (SLO), optical coherence tomography, and multifocal electroretinography. Following screening and examination, patients received an immediate intravitreal injection of the DEX implant, with an injection administered at the four-month mark. Hard exudate (HE) areas were measured utilizing SLO fundus imaging., Results: Total cholesterol, low-density lipoprotein, and triglyceride levels were found to be positively correlated with the presence of HE. Following surgical intervention, all patients demonstrated an improvement in BCVA. The mean BCVA increased from a preoperative measurement of 0.79 ± 0.04 to 0.39 ± 0.02 at the 6 month follow-up, indicating a statistically significant difference (p < 0.001). The baseline HE area for the entire patient cohort was 2.28 ± 0.22. One month post-operation, the HE area exhibited a slight increase to 2.27 ± 0.22. However, by the 6 month follow-up, the HE area had significantly decreased to 0.8 ± 0.87, representing a 35.09% reduction from the baseline measurement (p < 0.001). It is worth noting that Patient P1 did not exhibit a statistically significant difference between preoperative and six-month postoperative HE area (p = 0.032). Preoperative BCVA measurements for Group A and Group B were 0.81 ± 0.03 and 0.77 ± 0.03, respectively, with no statistically significant intergroup difference (p = 0.333). The baseline HE area for Group A was 2.61 ± 0.16, which decreased to 0.38 ± 0.20 at the six-month follow-up, representing a 14.60% reduction from the baseline total area. For Group B, the baseline HE area was measured at 1.95 ± 0.09, then decreasing to 1.21 ± 0.13 at the six-month follow-up, indicating a 62.05% reduction from the baseline total area. A statistically significant difference in the postoperative 6 month HE area was observed between Group A and Group B (p < 0.001). In Group A, the reduction in HE area (initial HE area-final HE area) was positively correlated with the improvement in P1 (initial P1-final P1) (r = 0.610, p = 0.004). In Group B, a similar positive correlation was found (initial HE area-final HE area with initial P1-final P1) (r = 0.488, p = 0.029). In Group B, the reduction in HE area (initial HE area-final HE area) correlated positively with the improvement in BCVA (initial BCVA-final BCVA) (r = 0.615, p = 0.004). Additionally, in Group B, the reduction in HE area (initial HE area-final HE area) was positively correlated with the improvement in CMT (initial CMT-final CMT) (r = -0.725, p< 0.001). Aggravated cataracts were observed in thirteen eyes during a follow-up examination 6 months later., Conclusion: HE formation is associated with lipid levels. Dexamethasone implants demonstrate effectiveness in reducing HE areas in the short term, reducing macular edema, improving retinal structure, and enhancing visual function. The incidence of postoperative complications such as cataracts and glaucoma remains low., (© 2024. The Author(s).)

The increasing focus on patient centricity in the pharmaceutical industry over the past decade and the changing healthcare landscape, driven by factors such as increased access to information, social media, and evolving patient demands, has necessitated a shift toward greater connectivity and understanding of patients' unique treatment needs. One pharmaceutical technology that has supported these efforts is long acting injectables (LAIs), which lower the administration frequency for the patient's provided convenience, better compliance, and hence better therapeutical treatment for the patients. Furthermore, patients with conditions like the human immunodeficiency virus and schizophrenia have positively expressed the desire for less frequent dosing, such as that obtained through LAI formulations. In this work, a comprehensive analysis of marketed LAIs across therapeutic classes and technologies is conducted. The analysis demonstrated an increasing number of new LAIs being brought to the market, recently most as aqueous suspensions and one as a solution, but many other technology platforms were applied as well, in particular, polymeric microspheres and in situ forming gels. The analysis across the technologies provided an insight into to the physicochemical properties the compounds had per technology class as well as knowledge of the excipients typically used within the individual formulation technology. The principle behind the formulation technologies was discussed with respect to the release mechanism, manufacturing approaches, and the possibility of defining predictive in vitro release methods to obtain in vitro in vivo correlations with an industrial angle. The gaps in the field are still numerous, including better systematic formulation and manufacturing investigations to get a better understanding of potential innovations, but also development of new polymers could facilitate the development of additional compounds. The biggest and most important gaps, however, seem to be the development of predictive in vitro dissolution methods utilizing pharmacopoeia described equipment to enable their use for product development and later in the product cycle for quality-based purposes.

Background: Uveitis leads to blindness in 10-15% of all cases in industrialized nations. The prevalence varies depending on the literature, ranging from 9 to 730 cases per 100,000 inhabitants. Local and systemic steroid applications, along with treatment involving immunomodulators, are the primary treatment options. In cases of chronic and refractory uveitis, especially with the manifestation of uveitic macular edema, intravitreal corticosteroids can contribute to reduce or completely replace systemic immunomodulatory therapy with disease-modifying antirheumatic drugs (DMARDs), biologics or corticosteroids., Objective: This review article presents the currently available intravitreal corticosteroid implants used in the treatment of noninfectious uveitis. The indications, effectiveness, and side effect profiles are discussed within the context of the current literature. A total of 6 randomized controlled studies about FAc and DEX implants with more than 100 patients were included in this review. One subgroup analysis from a multicentric randomized study with 315 patients has been included as well. The outcome is discussed in this article., Conclusion: The efficacy and safety profile of intravitreal corticosteroids in uveitic macular edema have been evaluated in several studies in recent years. In some studies, they have been compared to systemic treatment options. With long-acting corticosteroid implants the number of relapses can be reduced and the time interval between relapses can be prolonged. Short-acting corticosteroid implants represent a treatment option during acute uveitic activity. The adverse effects of corticosteroids can be well-controlled in most cases. In phakic and/or young patients, however, adverse effects (such as cataract development) should be discussed in depth before treatment initiation as most corticosteroids are applied as long-term treatment., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate changes in intraocular pressure following intravitreal dexamethasone implant injection, specifically in patients undergoing glaucoma filtration surgery., Methods: The degree of increase in intraocular pressure was compared retrospectively among three groups. Group 1 comprised patients who underwent prior glaucoma filtration surgery (54 eyes). Group 2 included patients with or suspected glaucoma without such surgical history (20 eyes). Group 3 included patients without glaucoma (33 eyes). Pressure measurements were taken before the injection and at 1, 2, 3, and 6 months post-injection. A subgroup analysis was performed for pressure > 35 mmHg, > 30 mmHg, > 25 mmHg, and a difference > 10 mmHg between the peak and baseline pressure., Results: Group 1 consistently displayed lower pressures compared with Group 2, with significant difference at both 1- and 6-month post-injections (15.09 mmHg vs. 18.10 mmHg, P = 0.042 and 13.91 mg vs. 17.25 mmHg, P = 0.040). The proportion of patients in Group 1 and Group 3 with pressures > 25 mmHg, > 30 mmHg, and a difference > 10 mmHg did not significantly differ (15.6% vs. 9.5%, P = 0.231; 3.1% vs. 2.3%, P = 0.867; and 17.1% vs. 7.1%, P = 0.231). Notably, Group 2 exhibited a significantly higher proportion within each category (> 25 mmHg, 24.0%; > 30 mmHg, 20.0%; > 10 mmHg difference, 28.0%)., Conclusion: Intravitreal dexamethasone implant did not increase the risk of elevated intraocular pressure in patients with a history of glaucoma filtration surgery compared with patients with suspected glaucoma; the risk was similar to those without glaucoma., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Melengestrol acetate (MGA) implants are a progestin-based reversible contraceptive used to manage fertility in animals. MGA implants are recommended for replacement every 2 years; however, reproduction may be suppressed longer if implants are not removed. In this study, we investigated whether the probability of reproducing (pR) differed among nonimplanted females, females with MGA implants removed, and females whose implants were not removed. In addition, since implant loss in hamadryas baboons is a concern, we explored whether female age, institution, implant placement year, implant location, or implant placement type (intramuscular vs. subcutaneous) differed for females whose implants were lost compared to those that were not. The pR differed significantly across all three treatment conditions with the nonimplanted group having the highest pR. The pR plateaued at 63% after 40 months for the implant-removed group compared to 96% after 84 months in the nonimplanted group. There was no reproduction after contraception if implants were not removed (7.83-45.53 months). In the nonimplanted group, pR was significantly higher for older and parous females. In terms of implant loss, we found that implant placement type was significantly associated with implant loss, such that there were fewer losses when implants were placed intramuscularly (IM) as compared to subcutaneously. Our results suggest that placing MGA implants IM is likely to reduce loss. When loss is prevented, MGA implants are an effective form of contraception and are reliably reversibly in most individuals when removed. However, if not removed, they can prevent reproduction longer than 2 years., (© 2024 Wiley Periodicals LLC.)

Purpose: To describe a case of peripapillary pachychoroid syndrome (PPS) in a diabetic patient with cystoid macular edema (CME), treated with intravitreal dexamethasone implant (IDI) injection. This report also illustrates the history of the disease after repeated IDI and dexamethasone topical treatment., Methods: A case report., Results: A 77-year old male patient with PPS and good diabetic control was treated with dexamethasone implant for CME. After an initial morphofunctional improvement associated with a first IDI, the disease relapsed after the second dexamethasone implant injection. This was associated with a significant increase in both intraretinal fluid and choroidal thickness, with subsequent visual acuity (VA) decrease. At this point, a topical dexamethasone treatment was performed and, despite a morphological improvement, VA worsened compared with baseline, likely because of anatomical damage., Conclusion: In this report, the importance of the recognition of PPS is underlined and the possible occurrence of a "rebound" effect due to repeated IDI is described., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To evaluate the long-term outcomes of patients with non-infectious uveitis treated with 0.19 mg fluocinolone acetonide insert (FAi) for up to 36 months in clinical practice., Methods: A retrospective study conducted at a single uveitis center., Results: Fifty eyes of 39 patients were included. Mean best corrected visual acuity (BCVA) and central retinal thickness (CRT) remained stable until month 36 after FAi implantation (61.04 vs. 70.25 letters and 370.8 vs. 332.5 µm, respectively). The recurrence rate was 34% (17 eyes) after 36 months, of which 82% (14 eyes) received high-dose corticosteroids before FAi. Mean intraocular pressure (IOP) remained unchanged (13.38 vs. 15.74 mmHg), while most phakic eyes (13 of 14 eyes) required cataract surgery., Conclusions: We show that FAi effectively prevents recurrences of non-infectious uveitis for up to three years in clinical practice, comparable with randomized clinical trials. Patients who received high-dose corticosteroids before FAi have an increased risk for early recurrence and should be considered for scheduled re-treatment.

Purpose: To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial)., Design: Multicenter, randomized, double-masked, sham-controlled, noninferiority trial., Participants: Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am, 10 am, and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am, 10 am, and 4 pm timepoints at baseline., Methods: Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193)., Main Outcome Measures: The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am, at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments., Results: Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis)., Conclusions: The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To assess the effectiveness of switching intravitreal dexamethasone implants (DEX-implant) from pro re nata (PRN) treatment regimen to a proactive regimen in patients with macular edema of diverse etiologies., Design: An observational, retrospective, uncontrolled, multicenter, national case series., Participants: Eighty-one eyes from 68 patients treated between October 2015 and June 2023 were included., Methods: This study included consecutive eyes treated with DEX-implant who were switched from a PRN regimen to a proactive regimen for diabetic macular edema (DME), retinal vein occlusion (RVO), noninfectious uveitis macular edema (UME; including postsurgical macular edema), and radiation maculopathy (RM)., Main Outcome Measures: The main outcome measures were change in the best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) at each visit., Results: According to the etiology, DME represented 49.4% of eyes, UME 24.3%, RVO 21.0%, and RM 6.2%. The mean (standard deviation [SD]) duration of follow-up under the PRN and proactive regimens was 20.6 (13.3) and 14.2 (10.3) months, respectively. Switching from a PRN to a proactive regimen significantly improved mean (SD) BCVA by 3.7 (12.9) ETDRS letters (P = 0.01) with a mean (SD) decrease in CMT of 108.0 (151.4) μm (P < 0.001). The proportion of visits with significant anatomic recurrence (> 50 μm) also decreased from 40.1% to 6.0% after switching to a proactive regimen (P < 0.001). The number of DEX-implant injections significantly increased during the proactive treatment period (P < 0.001), but the change in the number of visits was not significantly different (P = 0.2). The proactive treatment period was not associated with a significant increase in IOP (P = 0.6)., Conclusions: Switching to a proactive regimen in patients already treated with DEX-implant seems to significantly improve BCVA and CMT while maintaining stable IOP., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the clinical relevance of The European School for Advanced Studies in Ophthalmology (ESASO) classification in patients with diabetic macular edema (DME) after their first dexamethasone implant (DEXI) treatment., Methods: Retrospective real-world study conducted on consecutive DME patients who underwent DEXI treatment and were controlled at month-2. Subjects were initially classified according to the ESASO classification stages. The outcomes were anatomical biomarkers with spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA)., Results: A total of 128 patients were classified according to ESASO classification stages as early (7; 5.5%), advanced (100; 78.1%), and severe (21; 16.4%). At baseline, there were significant differences between stages in BCVA, central macular thickness (CMT), and tomography anatomical biomarkers (p < 0.05). Initial BCVA (logMAR) was 0.33 ± 0.10, 0.58 ± 0.34, and 0.71 ± 0.35 in the early, advanced, and severe stages, respectively (p < 0.05). At month-2, BCVA was 0.17 ± 0.15, 0.46 ± 0.29, and 0.69 ± 0.27 in those classified as early, advanced, and severe stages, respectively. At month-2, DME was resolved or improved in 6 (85.7%), 60 (60%), and 12 (60%) patients classified as early, advanced, and severe stages, respectively., Conclusions: There was a good correlation between BCVA and ESASO classification stages. Patients in the severe stage did not achieve visual acuity improvement over the study period., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Immediately following the Dobbs decision, Ohio prohibited abortion after the detection of fetal cardiac activity. We aimed to characterize changes in the uptake of long-acting reversible contraception (LARC) and permanent contraception following the abrupt enactment of restrictive abortion legislation., Study Design: We conducted a retrospective cohort study using electronic medical record data of patients aged 15 to 55 who underwent permanent contraception (tubal ligation, vasectomy) or LARC placement (intrauterine device, contraceptive implant) at a multihospital system in northeast Ohio from January 1, 2022 to Decemeber 31, 2022, 6 months before and after Dobbs. We compared procedure volumes and patient characteristics., Results: We identified 4247 tubal ligation and LARC procedures pre-Dobbs, including 725 (17.1%) permanent contraception and 3522 (82.9%) LARC. Post-Dobbs, the total number of tubal ligation and LARC procedures increased by 15.8% (4916), and there was a significant increase in the proportion of permanent contraception, (p < 0.001). Vasectomy volume increased by 33.3% post-Dobbs, from 1193 to 1590 procedures. Compared to pre-Dobbs, patients undergoing contraceptive procedures post-Dobbs were younger (tubal ligation and LARC, 30.9 median years [24.5, 36.8] vs 31.5 [25.2, 36.9], p = 0.011; vasectomy, median 36.6 years [32.9, 39.6] vs 37.2 [34.2, 40.4], p < 0.001) and more likely to report single relationship status (57.4% vs 55.9% for tubal ligation and LARC, p = 0.028% and 23.0% vs 18.1% for vasectomy, p = 0.002)., Conclusions: This study demonstrates increased uptake of contraceptive procedures following the Dobbs decision. This rise in permanent contraception suggests a relationship between abortion policy and contraceptive decision-making, especially among younger patients., Implications: Increased permanent and long-acting reversible contraception procedures following Dobbs reveal shifting contraceptive choices, particularly among younger individuals, indicating a connection between abortion policy and reproductive decisions., (Copyright © 2024 Elsevier Inc. All rights reserved.)