Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-Women's Endocrinology.

PURPOSE: To provide the latest scientific knowledge on the efficacy of inositols for improving reproductive disorders in women with and without polycystic ovary syndrome (PCOS) and to reach a consensus on their potential use through a Delphi-like process. METHODS: A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes. RESULTS: A total of eight consensus statements were drafted. Myo-inositol (Myo) supplementation can be used to improve menses irregularities and anovulation in PCOS. Myo supplementation can be used in subfertile women with or without PCOS to reduce the dose of r-FSH for ovarian stimulation during IVF, but it should not be used to increase the clinical pregnancy rate or live birth rate. Myo supplementation can be used in the primary prevention of gestational diabetes mellitus (GDM), but should not be used to improve pregnancy outcomes in women with GDM. Myo can be preconceptionally added to folic acid in women with a previous neural tube defects (NTD)-complicated pregnancy to reduce the risk of NTDs in newborns. Myo can be used during pregnancy to reduce the risk of macrosomia and neonatal hypoglycemia in mothers at risk of GDM. CONCLUSION: This consensus statement provides recommendations aimed at guiding healthcare practitioners in the use of inositols for the treatment or prevention of female reproductive disorders. More evidence-based data are needed to definitively establish the usefulness of Myo, the appropriate dosage, and to support the use of D-chiro-inositol (DCI) or a definitive Myo/DCI ratio.

3D Heads-up digital filters for cataract surgery and corneal transplantation.

PURPOSE: To describe the advantages of Ngenuity 3D digital filters for enhancing visualization during cataract and corneal transplant surgery. METHODS: All surgeries were performed by the same experienced surgeon (L.M.) using the Ngenuity 3D heads-up visualization system connected to a microscope. Images were simultaneously captured with and without the filter in each of the following phases: endothelial evaluation, capsulorhexis, capsule rupture, vitreous leak, cortex removal, visco removal, corneal suture, descemetorhexis, DMEK graft preparation and insertion. RESULTS: In cataract surgery, green and monochrome filters facilitate capsulorhexis in difficult situations by highlighting the anterior capsule and can improve visualization of a posterior capsular tear. The enhanced contrast of the monochrome filter is also useful for cortex and viscoelastic removal. In corneal surgery, the green filter highlights the rim of the DMEK graft during tissue preparation, the yellow filter enhances the contrast of the stained DMEK graft in the anterior chamber, the monochrome filter simplifies descemetorhexis by improving visualization of the Descemet/endothelial layer and allows a better view in red saturated images while performing sutures. CONCLUSIONS: Ngenuity digital filters have the potential to enhance tissue visualization during cataract and corneal surgeries, especially in poor visibility conditions.

High-Fluence Epithelium-off Accelerated Pulsed Corneal Cross-linking (15 mW/cm2; 7.2 J/cm2) for Pediatric Keratoconus: A 3-Year Retrospective Analysis.

PURPOSE: To assess the safety and efficacy of treatment and secondarily determine the topographic changes, visual outcomes, and demarcation line depth after high-fluence pulsed light accelerated cross-linking (ACXL) in pediatric patients (younger than 18 years) with progressive keratoconus. METHODS: This retrospective analysis included 32 eyes (25 children, aged 11 to 18 years), with progressive keratoconus treated with high-energy epithelium-off pulsed light ACXL (7.2 J/cm2, 15 mW/cm2, 12 minutes, 2 seconds on/1 second off). Corrected distance visual acuity (CDVA), Scheimpflug tomography, and anterior optical coherence tomography measurements were recorded preoperatively and 1, 2, and 3 years postoperatively. RESULTS: A total of 32 eyes were included. Significant CDVA improvement, pachymetry, and maximum keratometry reduction were found at all follow-up visits. Mean keratometric values remained stable, and astigmatism showed a mild worsening (< 0.25 D) with statistical significance at 1 and 3 years. Total aberration showed discordant results and coma aberration had a slight improvement without statistical significance. The demarcation line depth was 265 ± 26 µm. Three patients developed mild haze without visual acuity loss. None of the patients underwent a second CXL procedure. CONCLUSIONS: In pediatric patients, high-fluence epithelium-off pulsed light ACXL appears to be a safe and effective procedure to halt the progression of keratoconus, slightly improving the CDVA and keratometric values. [J Refract Surg. 2024;40(3):e148-e155.].

Non-Pathogenic Aspergillus oryzae Acute Exogenous Endophthalmitis after Penetrating Keratoplasty: The First Case Report in the Literature.

The authors report a singular case of post-operative exogenous fungal endophthalmitis caused by a non-pathogenic fungal agent: Aspergillus oryzae. A 75-year-old Caucasian woman with post-penetrating keratoplasty fungal endophthalmitis due to a nonpathogenic A. oryzae, resistant to the current azoles anti-fungal agents, was treated with subtotal vitrectomy, intravitreal injection, and systemic voriconazole therapy. Complete resolution of the endophthalmitis occurred after two subsequent intravitreal injections and a 2-month-long systemic delivery of voriconazole. The quick identification of the fungal agent allowed immediate and targeted therapy. In the article, the safety and efficacy of both systemic and intravitreal voriconazole treatments are discussed.

Binocular Visual Function Changes After Corneal Collagen Cross-linking in Patients With Keratoconus.

PURPOSE: High-order aberrations (HOAs) have been demonstrated to profoundly affect both visual acuity and stereoacuity in patients with keratoconus. Corneal collagen cross-linking (CXL) has been proven to significantly lower HOAs in keratoconus. Yet, to the present date, no evaluation of the effect of the procedure on stereopsis has been performed. The purpose of the study was to assess differences in binocular visual performance in patients with keratoconus before and after CXL. METHODS: Patients with keratoconus undergoing standard Dresden protocol epi-off CXL in the ophthalmology department of Policlinico Universitario Agostino Gemelli Hospital received slitlamp examination, uncorrected distance visual acuity and corrected distance visual acuity assessment, corneal tomography, Lang stereotest, TNO stereoacuity assessment, distance and near cover test, and Irvine test before surgery and 6 months after CXL. Stereopsis tests were performed with spectacle correction. RESULTS: The analysis included 30 patients (mean age 24.63 ± 3.49 years). The Lang test improved after treatment ( P 0.027), with 6 of 30 patients (20%) showing a positive Lang test before CXL compared with 16 of 30 patients (53.3%) after treatment. Moreover, TNO stereoacuity increased after treatment ( P 0.043), and 14 of 30 patients (46.7%) manifested an improvement of at least 250″ at the TNO test after CXL. In this subgroup of patients, total root mean square values decreased after treatment ( P < 0.001), whereas patients who did not manifest a clinically significant improvement in stereoacuity did not show a reduction in total root mean square values after CXL ( P = 0.11). The results of cover test and Irvine test did not vary after CXL. CONCLUSIONS: Patients with keratoconus showing a reduction of HOAs after CXL also manifest a significant improvement in stereoacuity after the treatment.

An Overview of Intraoperative OCT-Assisted Lamellar Corneal Transplants: A Game Changer?

Intraoperative optical coherence tomography (iOCT) is a noninvasive imaging technique that gives real-time dynamic feedback on surgical procedures. iOCT was first employed in vitreoretinal surgery, but successively served as a guidance in several anterior segment surgical approaches: keratoplasty, implantable Collamer lens (ICL) implantation, and cataract surgery. Among all of those approaches, the unbeatable features of iOCT are fully exploited in anterior and posterior lamellar keratoplasty, and the purpose of this review is to focus on the advantages and shortfalls of iOCT in these techniques, in order to assess whether this technology could be a real step forward. In deep anterior lamellar keratoplasty (DALK), iOCT is useful to evaluate the needle depth into the corneal stroma, the big bubble dissection plane, and residual stromal bed, thus aiding the standardization of the technique and the reduction of failures. In Descemet stripping automated endothelial keratoplasty (DSAEK), iOCT allowed for clear visibility of fluid at the graft/host interface, allowing for immediate rescue maneuvers and granting the best graft apposition. In Descemet membrane endothelial keratoplasty (DMEK), iOCT can track the lenticule unfolding in real time and assess graft orientation even in severe hazy corneas, thus optimizing surgical times, as well as avoiding the use of potentially hazardous exterior markers (such as the "S" stamp) and preventing unnecessary manipulation of the graft. Overall, the role of iOCT appeared crucial in several complicated cases, overcoming the difficulties of poor visualization in a fast, non-invasive way, thus raising this approach as possible gold standard for challenging conditions. Further improvements in the technology may enable autonomous centering and tracking, overcoming the current constraint of instrument-induced shadowing.

Combined Oral Contraception and Bicalutamide in Polycystic Ovary Syndrome and Severe Hirsutism: A Double-Blind Randomized Controlled Trial.

Context: Hirsutism often occurs in women with polycystic ovary syndrome (PCOS). The efficacy of oral contraceptive pill (OCP) plus antiandrogens in the treatment of its severe expression is controversial due to the lack of randomized, double-blind, long-term studies. Objective: The primary outcome was the reduction of hirsutism in PCOS women objectively measured by videodermoscopy on the androgen-sensitive skin areas assessed by the modified Ferriman and Gallwey (mF&G) total score, after 12 months of therapy with OCP + bicalutamide (BC) vs OCP plus placebo (P). The secondary outcomes were to evaluate tolerability of BC and body composition as well as the occurrence of adverse events. Design: An experimental, phase 3, prospective, multicenter, randomized, double-blind, P-controlled trial. Patients were evaluated at the baseline visit, at 6 and 12 months during treatment, and 6 months' posttreatment. Participants: Seventy women with classic PCOS (severe hirsutism, oligoanovulation, and ovarian polycystic ovarian morphology). Intervention: Patients received OCP + BC (50 mg/d) or OCP + P for 12 months. Results: The repeated measures analysis of variance showed that both treatments were effective in reducing hirsutism: The OCP + BC group had a higher reduction compared with the OCP + P group. No adverse effects were described during treatment except an increase in total cholesterol and low-density lipoprotein in the OCP + BC group. Conclusions: The association of OCP + BC is well tolerated and significantly more effective than OCP alone in treating severe hirsutism. We suggest a combined use of the videodermoscopic index and mF&G to evaluate the effects of androgen deprivation therapy for hirsutism.

Virilizing leydig-sertoli cell ovarian tumor associated with endometrioid carcinoma of the endometrium in a postmenopausal patient: case report and general considerations.

INTRODUCTION: Sertoli-Leydig cell tumors (SLCTs) are rare tumors mostly occurring in young women. Here we report an unusual case of a SLCT with simultaneous occurrence of endometrioid adenocarcinoma of the endometrium in a woman in menopause. CASE REPORT: A 67-year-old woman presented with progressive signs of virilization. Blood tests showed increased levels of testosterone, delta-4-androstenedione, and dehydroepiandrosterone (DHEA). DHEA-sulphate, 17ß-estradiol, estrone, and sex-hormone binding globulin serum levels were within the normal range. Magnetic resonance imaging revealed a solid mass of 2.7 × 2.9 cm in the right ovary set against the background of the uterus. The patient underwent bilateral salpingo-oophoretomy with hysterectomy. The mass in the right ovary was a differentiated SLCT. Incidentally, the endometrium revealed an endometrioid adenocacinoma. Following surgical treatment the plasma androgens dropped to normal levels, and signs and symptoms of virilization improved. CONCLUSION: SLCT should be suspected in postmenopausal women who present rapid progressive androgen excess symptoms with hyperandrogenemia.

Graft rejection after femtosecond laser--assisted deep anterior lamellar keratoplasty: report of 3 cases.

PURPOSE: To report 3 cases of stromal rejection after deep anterior lamellar keratoplasty (DALK) assisted by a femtosecond laser. METHODS: Three keratoconus eyes of 2 men (22 and 30 years old) and 1 woman (24 years old) who had DALK with a 60-kHz femtosecond laser developed intrastromal graft rejection with superficial and deep neovascularization after 6, 15, and 12 months, respectively. All patients underwent confocal microscopy and were treated with topical steroid therapy. RESULTS: In vivo confocal microscopy revealed cellular inflammatory infiltrates in the subepithelial and middle stroma of the donor lamella without involvement of the endothelium. Graft rejection was rapidly reversed with topical steroid therapy, and a clear cornea was restored in all cases. CONCLUSIONS: Graft rejection remains a significant complication of lamellar surgery but is associated with good tissue restoration and complete visual recovery.

Effect of epigallocatechin-gallate on inner retinal function in ocular hypertension and glaucoma: a short-term study by pattern electroretinogram.

BACKGROUND: Epigallocatechin-gallate (EGCG) is a powerful antioxidant with suggested neuroprotective action. The aim of this study was to evaluate the effect of short-term supplementation of EGCG on inner retinal function in ocular hypertension (OHT) and open-angle glaucoma (OAG). METHODS: Eighteen OHT and 18 OAG patients (perimetric mean deviation: >-10 dB) were randomly assigned to assume oral placebo or EGCG over a 3-month period in a randomized, placebo-controlled, double-blind, cross-over design clinical trial (clinicaltrials.gov identifier: NCT00476138). Pattern-evoked electroretinograms (PERGs) to 1.6 cycles/degree square-wave gratings, counterphased at 16 reversals/second, and standard automated perimetry (Humphrey 30-2) were assessed at the study entry (baseline), and after 3 months of placebo or EGCG. RESULTS: After EGCG, PERGs of OAG, but not OHT patients were increased in amplitude, compared either to baseline values (mean amplitude change: 0.06 log microV, p < 0.05) or to PERG amplitude values found in the same patients after placebo administration (mean change: -0.02 log microV, p not significant; difference between EGCG and placebo: 0.08 log microV, p < 0.05). In both OHT and OAG patients, standard automated perimetry did not show significant changes after either EGCG or placebo. In individual OAG patients, the magnitude of PERG amplitude increment after EGCG was inversely related (r = -0.8, p < 0.01) to corresponding baseline amplitudes. CONCLUSIONS: Although this study cannot provide evidence for long-term benefit of EGCG supplementation in OAG, and the observed effect is small, the results suggest that EGCG might favourably influence inner retinal function in eyes with early to moderately advanced glaucomatous damage.

Femtosecond laser-assisted lamellar keratoplasty: early results.

PURPOSE: To evaluate the outcomes and safety of lamellar keratoplasty (LK) assisted by a femtosecond laser. METHODS: Twenty-one eyes of 21 patients affected by different corneal pathologies (5 posttraumatic corneal scar, 3 postkeratitis corneal leucoma, and 13 keratoconus) underwent LK procedures by using a femtosecond laser. The mean thinnest corneal thickness, evaluated with ultrasound corneal pachymetry and with confocal microscopy, was 434.19 +/- 62.60 (SD) microm (range, 333-548 microm). Mean preoperative uncorrected visual acuity was 0.09 +/- 0.28 SD and mean preoperative best spectacle-corrected visual acuity was 0.28 +/- 0.15 SD. A femtosecond laser was used to perform corneal cuts on both donor and recipient corneas. The donor corneal lamella diameters were 0.20-mm larger and thicker than the recipient to restore a physiologic corneal thickness and shape: mean donor diameter was 8.34 +/- 0.28 mm (range, 8.2-8.7 mm) and mean thickness was 352 +/- 40.27 microm (range, 220-400 microm). Mean follow-up was 20.86 +/- 5.76 months (range, 12-30 months). RESULTS: Early postoperative evaluation showed a clear graft in all cases. A normal corneal pattern topography and a physiologic thickness (mean corneal pachymetry, 542.48 +/- 33.20 microm) and transparency were restored. Twelve months after surgery, the mean postoperative uncorrected visual acuity was 0.45 +/- 0.34 SD, and the mean best spectacle-corrected visual acuity was 0.63 +/- 0.16 SD. CONCLUSIONS: Although the numbers in our study are small, our early results indicate that femtosecond laser-assisted lamellar keratoplasty shows promise as a safe and effective surgical choice in the treatment of various corneal pathologies.