Women and men with distressing low sexual desire exhibit sexually dimorphic brain processing.

Distressing low sexual desire, termed Hypoactive Sexual Desire Disorder (HSDD), affects approximately 10% of women and 8% of men. In women, the 'top-down' theory of HSDD describes hyperactivity in higher-level cognitive brain regions, suppressing lower-level emotional/sexual brain areas. However, it is unknown how this neurofunctional disturbance compares to HSDD in men. To investigate this, we employed task-based functional MRI in 32 women and 32 men with HSDD to measure sexual-brain processing during sexual versus non-sexual videos, as well as psychometric questionnaires to assess sexual desire/arousal. We demonstrate that women had greater activation in higher-level and lower-level brain regions, compared to men. Indeed, women who had greater hypothalamic activation in response to sexual videos, reported higher psychometric scores in the evaluative (r = 0.55, P = 0.001), motivational (r = 0.56, P = 0.003), and physiological (r = 0.57, P = 0.0006) domains of sexual desire and arousal after watching the sexual videos in the scanner. By contrast, no similar correlations were observed in men. Taken together, this is the first direct comparison of the neural correlates of distressing low sexual desire between women and men. The data supports the 'top-down' theory of HSDD in women, whereas in men HSDD appears to be associated with different neurofunctional processes.

Quantifying the variability in the assessment of reproductive hormone levels.

OBJECTIVE: To quantify how representative a single measure of reproductive hormone level is of the daily hormonal profile using data from detailed hormonal sampling in the saline placebo-treated arm conducted over several hours. DESIGN: Retrospective analysis of data from previous interventional research studies evaluating reproductive hormones. SETTING: Clinical Research Facility at a tertiary reproductive endocrinology centre at Imperial College Hospital NHS Foundation Trust. PATIENTS: Overall, 266 individuals, including healthy men and women (n = 142) and those with reproductive disorders and states (n = 124 [11 with functional hypothalamic amenorrhoea, 6 with polycystic ovary syndrome, 62 women and 32 men with hypoactive sexual desire disorder, and 13 postmenopausal women]), were included in the analysis. INTERVENTIONS: Data from 266 individuals who had undergone detailed hormonal sampling in the saline placebo-treated arms of previous research studies was used to quantify the variability in reproductive hormones because of pulsatile secretion, diurnal variation, and feeding using coefficient of variation (CV) and entropy. MAIN OUTCOME MEASURES: The ability of a single measure of reproductive hormone level to quantify the variability in reproductive hormone levels because of pulsatile secretion, diurnal variation, and nutrient intake. RESULTS: The initial morning value of reproductive hormone levels was typically higher than the mean value throughout the day (percentage decrease from initial morning measure to daily mean: luteinizing hormone level 18.4%, follicle-stimulating hormone level 9.7%, testosterone level 9.2%, and estradiol level 2.1%). Luteinizing hormone level was the most variable (CV 28%), followed by sex-steroid hormone levels (testosterone level 12% and estradiol level 13%), whereas follicle-stimulating hormone level was the least variable reproductive hormone (CV 8%). In healthy men, testosterone levels fell between 9:00 am and 5:00 pm by 14.9% (95% confidence interval 4.2, 25.5%), although morning levels correlated with (and could be predicted from) late afternoon levels in the same individual (r2 = 0.53, P<.0001). Testosterone levels were reduced more after a mixed meal (by 34.3%) than during ad libitum feeding (9.5%), after an oral glucose load (6.0%), or an intravenous glucose load (7.4%). CONCLUSION: Quantification of the variability of a single measure of reproductive hormone levels informs the reliability of reproductive hormone assessment.

Obesity-Related Hypogonadism in Women.

Obesity-related hypogonadotropic hypogonadism is a well-characterized condition in men (termed male obesity-related secondary hypogonadism; MOSH); however, an equivalent condition has not been as clearly described in women. The prevalence of polycystic ovary syndrome (PCOS) is known to increase with obesity, but PCOS is more typically characterized by increased gonadotropin-releasing hormone (GnRH) (and by proxy luteinizing hormone; LH) pulsatility, rather than by the reduced gonadotropin levels observed in MOSH. Notably, LH levels and LH pulse amplitude are reduced with obesity, both in women with and without PCOS, suggesting that an obesity-related secondary hypogonadism may also exist in women akin to MOSH in men. Herein, we examine the evidence for the existence of a putative non-PCOS "female obesity-related secondary hypogonadism" (FOSH). We précis possible underlying mechanisms for the occurrence of hypogonadism in this context and consider how such mechanisms differ from MOSH in men, and from PCOS in women without obesity. In this review, we consider relevant etiological factors that are altered in obesity and that could impact on GnRH pulsatility to ascertain whether they could contribute to obesity-related secondary hypogonadism including: anti-Müllerian hormone, androgen, insulin, fatty acid, adiponectin, and leptin. More precise phenotyping of hypogonadism in women with obesity could provide further validation for non-PCOS FOSH and preface the ability to define/investigate such a condition.

Corneal Collagen Cross-Linking for Late Onset Progressive Keratoconus in Iridocorneal Endothelial Syndrome.

PURPOSE: The aim of this study was to report the first case of successful use of corneal collagen cross-linking (CXL) to halt the progression of keratoconus in a patient with concurrent iridocorneal endothelial (ICE) syndrome. METHODS: A 30-year-old White man was referred to our subspecialty corneal clinic for further investigation of right corectopia. The patient was asymptomatic and was otherwise fit. Slit-lamp examination revealed a right oval-shaped pupil decentered superiorly, a transillumination defect at the 5-o'clock position, minimal gutta-like changes in the corneal endothelium, and few inferior peripheral anterior synechiae. Dilated fundoscopy was normal in both eyes, with healthy optic discs, maculae, and peripheral retinae. Specular microscopy and slit-lamp findings suggested ICE syndrome. Subsequent investigation with corneal tomography showed progressive signs of inferior corneal ectasia with steepening, and thinning in the right eye, consistent with keratoconus. The left eye was unremarkable. RESULTS: Epithelium-off accelerated corneal CXL was performed in the affected eye. Early post-CXL follow-up (1 week) was unremarkable, and further follow-ups were arranged at 3, 6, 12, and 24 months, respectively. In subsequent reviews, the patient's vision and corneal tomography findings were stable. CONCLUSIONS: We describe the first case of corneal CXL for progressive keratoconus with ICE syndrome. co-existing keratoconus and ICE syndrome can occur, and corneal cross-linking was used successfully in this case to halt keratoconus progression. However, further studies will need to establish the impact of epithelium-off corneal cross-linking, especially in more severely affected eyes.

Derivation and comparison of formulae for the adjustment of total calcium.

Background: Free ionized calcium (Ca2+) is the biologically active component of total calcium (TCa) and hence responsible for its biological action. TCa is routinely adjusted for albumin using several formulae (e.g. James, Orell, Payne and Berry) to more closely reflect Ca2+. Here, we derive a novel formula to estimate Ca2+ and compare its performance to established formulae. Methods: Cohort for prediction of Ca2+: 2806 serum samples (TCa) taken contemporaneously with blood gas samples (Ca2+) at Imperial College Healthcare NHS Trust were used to derive formulae to estimate Ca2+ using multivariable linear regression. Cohort for prediction of PTH: Performance of novel and existing formulae to predict PTH in 5510 patients was determined by Spearman correlation. Results: Ca2+ prediction Cohort: Adjusted calcium (r2 = 0.269) was less strongly associated with Ca2+, than TCa (r2 = 0.314). Prediction of Ca2+ from a newly derived formula incorporating TCa, potassium, albumin, and hematocrit had an improved r2 of 0.327, whereas inclusion of all available parameters increased the r2 further to 0.364. Of the established formulae, James performed best in predicting Ca2+ (r2 = 0.27). PTH prediction cohort: Berry resulted in higher whereas Orell in lower adjusted calcium levels. Prediction of PTH was strongest in the setting of hypercalcemia, with James having the highest Spearman correlation coefficient (+0.496) similar to including all parameters (+0.499). Conclusion: Adjustment of calcium for albumin using established formulae does not always outperform unadjusted TCa in the reflection of Ca2+. Further prospective studies are needed to optimise adjustment of TCa and to establish bounds for validity.

Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.

Importance: The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior. Objective: To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD. Design, Setting, and Participants: This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021. Interventions: Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo. Main Outcomes and Measures: Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal. Results: Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02). Conclusions and Relevance: Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire. Trial Registration: isrctn.org Identifier: ISRCTN17271094.

Endocrine Responses to Triptorelin in Healthy Women, Women With Polycystic Ovary Syndrome, and Women With Hypothalamic Amenorrhea.

CONTEXT: Limited data exist regarding whether the endocrine response to the gonadotropin-releasing hormone receptor agonist (GnRHa) triptorelin differs in women with polycystic ovary syndrome (PCOS) compared with healthy women or those with hypothalamic amenorrhea (HA). OBJECTIVE: We compared the gonadotropin response to triptorelin in healthy women, women with PCOS, or those with HA without ovarian stimulation, and in women with or without polycystic ovaries undergoing oocyte donation cycles after ovarian stimulation. METHODS: The change in serum gonadotropin levels was determined in (1) a prospective single-blinded placebo-controlled study to determine the endocrine profile of triptorelin (0.2 mg) or saline-placebo in healthy women, women with PCOS, and those with HA, without ovarian stimulation; and (2) a retrospective analysis from a dose-finding randomized controlled trial of triptorelin (0.2-0.4 mg) in oocyte donation cycles after ovarian stimulation. RESULTS: In Study 1, triptorelin induced an increase in serum luteinizing hormone (LH) of similar amplitude in all women (mean peak LH: healthy, 52.3; PCOS, 46.2; HA, 41.3 IU/L). The AUC of change in serum follicle-stimulating hormone (FSH) was attenuated in women with PCOS compared with healthy women and women with HA (median AUC of change in serum FSH: PCOS, 127.2; healthy, 253.8; HA, 326.7 IU.h/L; P = 0.0005). In Study 2, FSH levels 4 hours after triptorelin were reduced in women with at least one polycystic morphology ovary (n = 60) vs normal morphology ovaries (n = 91) (34.0 vs 42.3 IU/L; P = 0.0003). Serum anti-Müllerian hormone (AMH) was negatively associated with the increase in FSH after triptorelin, both with and without ovarian stimulation. CONCLUSION: FSH response to triptorelin was attenuated in women with polycystic ovaries, both with and without ovarian stimulation, and was negatively related to AMH levels.

Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men.

Background: Delayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with "red flag" features of CHH commonly overlooked. Thus, several markers have been evaluated in both the basal state or after stimulation e.g. with gonadotrophin releasing hormone agonist (GnRHa).Insulin-like peptide 3 (INSL3) is a constitutive secretory product of Leydig cells and thus a possible candidate marker, but there have been limited data examining its role in distinguishing CDGP from CHH. In this manuscript, we assess INSL3 and inhibin B (INB) in two cohorts: 1. Adolescent boys with delayed puberty due to CDGP or CHH and 2. Adult men, both eugonadal and having CHH. Materials and methods: Retrospective cohort studies of 60 boys with CDGP or CHH, as well as 44 adult men who were either eugonadal or had CHH, in whom INSL3, INB, testosterone and gonadotrophins were measured. Cohort 1: Boys with delayed puberty aged 13-17 years (51 with CDGP and 9 with CHH) who had GnRHa stimulation (subcutaneous triptorelin 100mcg), previously reported with respect to INB. Cohort 2: Adult cohort of 44 men (22 eugonadal men and 22 men with CHH), previously reported with respect to gonadotrophin responses to kisspeptin-54. Results: Median INSL3 was higher in boys with CDGP than CHH (0.35 vs 0.15 ng/ml; p=0.0002). Similarly, in adult men, median INSL3 was higher in eugonadal men than CHH (1.08 vs 0.05 ng/ml; p<0.0001). However, INSL3 more accurately differentiated CHH in adult men than in boys with delayed puberty (auROC with 95% CI in adult men: 100%, 100-100%; boys with delayed puberty: 86.7%, 77.7-95.7%).Median INB was higher in boys with CDGP than CHH (182 vs 59 pg/ml; p<0.0001). Likewise, in adult men, median INB was higher in eugonadal men than CHH (170 vs 36.5 pg/ml; p<0.0001). INB performed better than INSL3 in differentiating CHH in boys with delayed puberty (auROC 98.5%, 95.9-100%), than in adult men (auROC 93.9%, 87.2-100%). Conclusion: INSL3 better identifies CHH in adult men, whereas INB better identifies CHH in boys with delayed puberty.

Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder.

BACKGROUNDHypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODSUsing psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTSMC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSIONThese data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATIONClinicalTrials.gov NCT04179734.FUNDINGThis is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (CS-2018-18-ST2-002 and RP-2014-05-001).

Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men.

CONTEXT: Osteoporosis results from disturbances in bone formation and resorption. Recent nonhuman data suggest that the reproductive hormone kisspeptin directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown. OBJECTIVE: To assess the effects of kisspeptin on human bone metabolism in vitro and in vivo. METHODS: In vitro study: of Mono- and cocultures of human osteoblasts and osteoclasts treated with kisspeptin. Clinical study: Randomized, placebo-controlled, double-blind, 2-way crossover clinical study in 26 men investigating the effects of acute kisspeptin administration (90 minutes) on human bone metabolism, with blood sampling every 30 minutes to +90 minutes. Cells for the in vitro study were from 12 male blood donors and 8 patients undergoing hip replacement surgery. Twenty-six healthy eugonadal men (age 26.8 ±â€…5.8 years) were included in the clinical study. The intervention was Kisspeptin (vs placebo) administration. The main outcome measures were changes in bone parameters and turnover markers. RESULTS: Incubation with kisspeptin in vitro increased alkaline phosphatase levels in human bone marrow mesenchymal stem cells by 41.1% (P = .0022), and robustly inhibited osteoclastic resorptive activity by up to 53.4% (P < .0001), in a dose-dependent manner. Kisspeptin administration to healthy men increased osteoblast activity, as evidenced by a 20.3% maximal increase in total osteocalcin (P = .021) and 24.3% maximal increase in carboxylated osteocalcin levels (P = .014). CONCLUSION: Collectively, these data provide the first human evidence that kisspeptin promotes osteogenic differentiation of osteoblast progenitors and inhibits bone resorption in vitro. Furthermore, kisspeptin acutely increases the bone formation marker osteocalcin but not resorption markers in healthy men, independent of downstream sex steroid levels. Kisspeptin could therefore have clinical therapeutic application in the treatment of osteoporosis.

'Posture-Less' DMEK: Is Posturing After Descemet Membrane Endothelial Keratoplasty Actually Necessary?

PURPOSE: To evaluate the clinical results of Descemet membrane endothelial keratoplasty (DMEK) without any intraoperative or postoperative posturing. DESIGN: Retrospective, noncomparative, and interventional case series. METHODS: One hundred thirty-four (134) consecutive eyes of 101 patients requiring DMEK for any cause of endothelial failure were included. Descemet membrane endothelial keratoplasty was performed with an intraoperative inferior PI. After unscrolling and centration of the graft, the anterior chamber was near completely filled with 20% SF6. After filling the eye with gas there was no intraoperative tamponade time, and patients did not posture postoperatively. Main outcome measures were: graft detachment rate, rebubbling rate, primary and secondary failure rates, rejection rate, intraoperative and postoperative complications, and visual acuity 3 and 12 months after surgery. RESULTS: Five of 134 (3.7%) developed graft detachment greater than one-third of the graft area, and 19 of 134 (14.2%) developed graft detachment less than one-third of the graft area. A rebubble procedure was performed in 19 of 134 (14.2%); of those, the average number of rebubbling procedures performed was 1.13 (range, 1-2). Primary failure occurred in 6 of 134 (4.5%).Twelve-month graft survival occurred in 122 of 134 eyes (91.0%), with secondary failure within the first 12 months accounting for failure of 6 of 134 (4.5%). Nine of 134 (6.7%) cases had a recorded episode of endothelial rejection. The average time for rejection episode was 9.5 months (range, 1-20 months) after surgery. CONCLUSIONS: A total of 134 'posture-less' DMEKs did not suffer very high rates of graft detachment, rebubbling, or other postoperative complications, even with immediate erect posturing after surgery.

Multifocal IOL explantation in patients with opaque lentis after refractive lens exchange.

PURPOSE: We describe the outcomes of intraocular lens (IOL) explantation in a cluster of opaque multifocal Lentis LS-313 following refractive lens exchange (RLE). METHODS: Single-centre, single-surgeon, retrospective case series. RESULTS: The study enrolled 10 eyes of 10 patients, 6 male and 4 female. All patients had uneventful RLE with multifocal IOL implantation. The mean patient age at the time of RLE was 53 years ± 2.52 (SD). Two eyes had YAG laser capsulotomy prior to explantation. The mean interval between the initial RLE and IOL explantation was 5.4 years ± 1.4 (SD). IOL exchange was performed in all eyes in one procedure. Five eyes had in the bag hydrophobic acrylic IOL (3 multifocal and 2 monofocal), three eyes had 3-piece hydrophobic acrylic IOL in the ciliary sulcus and two had an anterior chamber IOL. Intraoperatively one patient had weak zonules and two patients had zonular dehiscence and required anterior vitrectomy. The mean preoperative CDVA was 0.25 ± 0.15 (SD) logMAR and at the final follow-up, improved to 0.00 ± 0.07 (SD) logMAR (p < 0.01). Light microscopy with von Kossa stain confirmed IOL calcification. No postoperative complications were recorded. CONCLUSIONS: IOL exchange appears to be a feasible and safe surgical option for multifocal IOL opacification. However, patients must be warned of additional intraoperative risks including zonular dialysis, vitreous loss, retinal detachment and need for potential scleral or iris fixated IOL or anterior chamber IOL (ACIOL) with its associated sequel of complications. Moreover, YAG laser capsulotomy should be considered carefully as it increases the chances of intraoperative complications and restricts the surgical options of secondary IOL insertion such as in-the-bag IOL exchange with MFIOL.

Changes in Circulating Kisspeptin Levels During Each Trimester in Women With Antenatal Complications.

CONTEXT: Antenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all 3 trimesters in women with antenatal complications. OBJECTIVE: We aimed to assess whether kisspeptin levels are altered in women with antenatal complications. METHODS: Women with antenatal complications (n = 105) and those with uncomplicated pregnancies (n = 265) underwent serial ultrasound scans and blood sampling at the Early Pregnancy Assessment Unit at Hammersmith Hospital, UK, at least once during each trimester (March 2014 to March 2017). The women with antenatal complications (HDP [n = 32], FGR [n = 17], GDM [n = 35], PTB [n = 11], and multiple complications [n=10]) provided 373 blood samples and the controls provided 930 samples. Differences in circulating kisspeptin levels were assessed. RESULTS: Third-trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking, and parity were increased by 30% (95% CI, 16%-47%; P < 0.0001), and of FGR were reduced by 28% (95% CI, 4-46%; P = 0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (P = 0.014) and lower in those with GDM (P = 0.020), but not significantly on multivariable analysis. CONCLUSION: We delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.

"The Spinning Technique" for Unfolding Tightly Scrolled DMEK Grafts.

PURPOSE: We present a no-touch Descemet membrane endothelial keratoplasty (DMEK) technique which assists in unfolding of tightly scrolled grafts from young donors. METHODS: The technique was developed following a wet-laboratory experiment using human corneas created to observe the behavior of the graft during spinning within the artificial anterior chamber. This approach involves injecting short bursts of balanced salt solution to make the scroll spin continuously in a 360-degree manner. Spinning of the graft over the surface is accompanied by rotation on its horizontal axis resulting in opening in the correct orientation. Unfolding is then completed with standard bimanual tapping maneuvers. The spinning technique was then performed in 4 patients who all had tight DMEK scrolls from young donors. RESULTS: The wet laboratory confirmed that directed jets of fluid to generate spinning and rotation open the graft in the correct orientation in most occasions. All 4 cases in this study received grafts from young donors (range 37-48 years old), and the technique achieved rapid unfolding with no complications. Two of our patients had glaucoma drainage devices, 1 had anterior chamber intraocular lens, and all other cases had clear corneas and good endothelial cell count after the 1-year follow-up. CONCLUSIONS: Our novel technique provides a safe and effective method to unscroll tight DMEK grafts that surgeons could incorporate into their armamentarium. Success is optimized by slightly undersizing the graft (7.5-8.0 mm).

Effect of surgical abstinence on the risk for posterior capsule rupture during cataract surgery.

PURPOSE: To evaluate the impact of surgery restrictions on cataract surgery performance. SETTING: Moorfields Eye Hospital, NHS Foundation Trust, London, United Kingdom. DESIGN: Retrospective, observational cross-sectional study. METHODS: A single-center, retrospective review of all patients who underwent phacoemulsification surgery at Moorfields Eye Hospital between September 2019 and January 2021 was conducted. The main outcome measure was posterior capsule rupture (PCR) rate before and after COVID-19-imposed restrictions to elective cataract surgery. RESULTS: A total of 15 688 surgeries were performed by 256 different surgeons in the study period. In the prerestriction period (September 2019 to March 2020), the PCR rate was 0.99%, whereas in the 19-week postrestriction period, the PCR rate spiked to 1.62% (odds ratio 1.65; P = .001; CI 1.24 to 2.20; relative risk: 1.64). CONCLUSIONS: The COVID-19 pandemic provided a unique opportunity to assess a large group of surgeons' performances after prolonged surgical abstinence. A 19-week restriction period in surgical activity showed an increased incidence of PCR complications. This is relevant because it can concern any surgeon on the extended time off from work such as sick, sabbatical, research, and parental leave. Supporting strategies should be implemented by associated regulators to minimize this negative impact.

Corneal Perforation in Patients Under Treatment With Dupilumab for Atopic Dermatitis.

PURPOSE: We report, for the first time, 2 cases of corneal ulceration and perforation after treatment with dupilumab for atopic dermatitis. METHODS: A 30-year-old woman and a 44-year-old man developed unilateral severe corneal ulceration and perforation while on dupilumab therapy after 3 and 9 months, respectively. RESULTS: Corneal cultures were negative in both cases except for scanty growth of Staphylococcus species on enrichment. Both cases progressed to perforation despite intensive topical antibiotic treatment. The first case required a tectonic keratoplasty to restore globe integrity after failed attempts of corneal gluing and multilayer amniotic membrane transplantation, and the second case was managed successfully with a cyanoacrylate glue patch. CONCLUSIONS: Although there have been previous reports of conjunctival injection and dry eye after dupilumab, these are the first 2 reports of corneal ulceration with rapid progression to perforation in patients under treatment with dupilumab. The underlying pathophysiology for ulcerative keratitis in these cases remains unknown, but there is no doubt that cessation of dupilumab prevented progression of the melting. Severe ocular symptoms while on dupilumab require a prompt discussion with the dermatology team to potentially switch treatment and halt further keratitis progression.