In vivo confocal microscopy study of corneal nerve alterations in children and youths with Type 1 diabetes.

OBJECTIVE: To determine whether children and youths with Type 1 diabetes (T1D) have early alterations of the corneal subbasal nerve plexus detectable with in vivo confocal microscopy (IVCM) and to investigate the role of longitudinally measured major risk factors for diabetes complications associated with these alterations. METHODS: One hundred and fifty children and youths with T1D and 51 age-matched controls were enrolled and underwent IVCM. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal fiber total branch density (CTBD), and corneal fiber fractal dimension (CNFrD) were measured. Risk factors for diabetes complications (blood pressure, BMI, HbA1c, lipoproteins, urinary albumin-creatinine ratio) were recorded at IVCM and longitudinally since T1D onset. Unpaired t-test was used to compare variables between the groups. Multiple regression models were calculated using IVCM parameters as dependent variables and risk factors as independent variables. RESULTS: All IVCM parameters, except CTBD, were significantly lower in the T1D patients. Glycometabolic control (HbA1c, visit-to-visit HbA1c variability, and mean HbA1c), and blood pressure were inversely correlated with IVCM parameters. Multiple regression showed that part of the variability in CNFL, CNFD, CTBD, and CNFraD was explained by HbA1c, blood pressure percentiles and age at IVCM examination, independent of diabetes duration, BMI percentile and LDL cholesterol. Comparable results were obtained using the mean value of risk factors measured longitudinally since T1D onset. CONCLUSIONS: Early signs of corneal nerve degeneration were found in children and youths with T1D. Glycometabolic control and blood pressure were the major risk factors for these alterations.

Gender medicine in corneal transplantation: influence of sex mismatch on rejection episodes and graft survival in a prospective cohort of patients.

To evaluate the effect of donor-to-recipient sex mismatched (male donor corneas to female recipients) on the incidence of rejection episodes and failures up to 1 year after corneal transplantation. Prospective observational cohort study, with donor corneas randomly assigned and surgeons blind to the sex of donor. A unique eye bank retrieved and selected the donor corneas transplanted in 4 ophthalmic units in patients with clinical indication for primary or repeated keratoplasty for optical reasons, perforating or lamellar, either anterior or posterior. Rejection episode defined as any reversible or irreversible endothelial, epithelial or stromal sign, with or without development of corneal edema, and graft failure as a permanently cloudy graft or a regraft for any reason detected or acknowledged during a postoperative ophthalmic visit at any time up to 1 year after surgery were recorded.156 (28.6%) patients resulted donor-to-recipient gender mismatched for H-Y antigen (male donor to female recipient). During the 12 months follow-up, 83 (14.7%, 95% CI 12.0-17.9) grafts showed at least 1 rejection episode and 17 (3.2%, 95% CI 2.0-5.0) failed after immune rejection, among 54 (9.6%, 95% CI 7.4-12.3) grafts failed for all causes. No significant differences between matched and mismatched patients were found for cumulative incidence of both rejection episodes (15.2% and 13.5%) and graft failures following rejection (3.2% and 2.6%), respectively. Multivariable analyses showed that H-Y matching either is not a predictive factor for rejection or graft failure nor seems to influence incidence of failures on respect to patient's risk category. The lack of influence of donor-to-recipient mismatched on the rate of rejections and graft failures resulting from this study do not support the adoption of donor-recipient matching in the allocation of corneas for transplantation.

Eight months follow-up of corneal nerves and sensitivity after treatment with cenegermin for neurotrophic keratopathy.

BACKGROUD: Cenegermin (Oxervate, Dompè Farmaceutici, Milan, IT), a recombinant human NGF, is a potentially healing new drug for neurotrophic keratopathy (NK), a rare but challenging disease affecting the cornea. To date, studies that evaluate its mid-term effect on corneal nerves and sensitivity are lacking. OBJECTIVE: To evaluate the recovery and morphology of subbasal corneal nerves in patients treated with Cenegermin for NK and assess their correlation with corneal sensitivity. METHODS: This prospective, observational case series study was carried out between May 2018 and August 2020 at the Ophthalmic Clinic of the University of Verona. Clinical evaluation, sensitivity, and in vivo confocal microscopy (IVCM) were performed in the central and all four corneal sectors at baseline, the end of therapy (8 weeks), and 2, 4, and 8 months after therapy. Consecutive patients with NK (stage 2-3), treated with Cenegermin (1 drop 6 times daily for 8 weeks), were enrolled. During each visit, Corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD), corneal nerve fiber fractal dimension (CNFraD) and Cochet-Bonnet esthesiometry (CBE) were measured. RESULTS: We enrolled 18 patients. Complete NK healing was noted in 14/18(78%) patients after 8 weeks of treatment; then in 14(78%), 15(83%), and 13(72%) patients at 2-, 4-, and 8-months, respectively. Starting at 8 weeks through 4-month follow-up there was progressive improvement in CBE in all corneal sectors (p ≤ 0.01), which continued thereafter. There was significant corneal nerve regrowth especially in the peripheral cornea: centripetal progression starting at 8 weeks (CNFL and CNFrad) and significant branching starting at 2 months (CTBD), which continued through to the end of follow up. Sector-coupled IVCM and CBE findings correlated at all evaluations (all r ≥ 0.62 starting at 2 months, with highest values in the peripheral sectors). CONCLUSIONS: After Cenegermin we observed a subbasal corneal nerve regeneration, a recovery of sensitivity and a lasting epithelial healing, suggesting that the effect of its action persists several months after discontinuation in patients with NK.

Effects of oral function on pupil response: a new view on bruxism pathophysiology.

BACKGROUND: There is increasing evidence of the influence of the oropharyngeal stimulations on the autonomic nervous system and an easy approach to evaluate the balance between parasympathetic and sympathetic system is the measurement of the pupil diameter. The aim of this analytic observational study is to define the effects of clenching and swallowing on pupil diameter, and how an oral appliance can affect the outcome of these tasks, to establish their influence on the sympathetic-parasympathetic balance. METHODS: We measured the pupil diameter in 30 healthy subjects during clenching and swallowing, both with and without oral appliance. We compared the results with the mandibular rest position. The respective positions with and without oral appliance were also compared. RESULTS: Pupillometry showed a mydriatic effect of swallowing (rest 6.94 mm, swallowing 7.26 mm, P=0.04) and oral appliance, more relevant in scotopic conditions. On the contrary, clenching seemed to enhance miosis, especially in intense brightness condition (rest 3.95 mm, clenching 3.83 mm, P=0.02). CONCLUSIONS: Swallowing and oral appliance facilitate the sympathetic system, while clenching activates the parasympathetic branch. We argue that probably the locus coeruleus is the main hub. These results could have practical implications in bruxism physiology, because it could be an attempt to counteract the activation of the sympathetic system.

Reduced minimum rim width of optic nerve head: a potential early marker of retinal neurodegeneration in children and adolescents with type 1 diabetes.

AIMS: To determine whether early retinal neurodegenerative changes in pediatric patients with type 1 diabetes (T1D) can be detected by spectral domain-optical coherence tomography (SD-OCT) and whether such changes are associated with risk factors for T1D complications. METHODS: A total of 147 T1D children/adolescents and 51 healthy controls underwent SD-OCT. Spherical refractive error (SRE), macular total retinal thickness (TRT), ganglion cell layer (GCL), retinal nerve fiber layer (RNFL), minimum rim width (MRW), and Bruch's membrane opening area (BMOA) were measured. Clinical and biochemical parameters were recorded at the time of SD-OCT and starting at T1D onset. Multiple regression models were calculated using SD-OCT parameters as dependent and risk factors as independent variables. RESULTS: MRW was significantly thinner in the T1D patients (global MRW:361.58vs386.33 µm; p = 0.009), while RNFL and macular parameters were similar for both groups. MRW was inversely correlated with mean HbA1c (r ≥ -0.180, p < 0.05). Multiple regression showed that part of the variability in MRW was explained by HbA1c and BMOA (R2 = 0.21; p < 0.001), independent of other cardiometabolic risk factors. CONCLUSIONS: MRW reduction could be a potential early marker of retinal neurodegeneration detectable in pediatric patients with T1D. The association between MRW and mean HbA1c suggests that glucometabolic control may affect early retinal neurodegeneration starting in childhood.

Obstructive Sleep Apnea Assessed by Overnight Polysomnography in Patients With Keratoconus.

PURPOSE: To determine the prevalence of obstructive sleep apnea (OSA) in patients with keratoconus (KCN) and to evaluate the association between the severity of KCN and OSA. METHODS: OSA was diagnosed with an overnight home sleep apnea test. As estimated by home monitoring, an apnea-hypopnea index threshold of ≥5 sleep-related obstructive breathing events per hour was considered suggestive of OSA. For grading KCN severity (Amsler-Krumeich classification), slit-lamp biomicroscopy, corneal topography, and pachymetry measurements were performed. Preoperative measurements were included in the analysis for patients who had undergone surgery for KCN. RESULTS: The study sample consisted of 50 consecutively enrolled patients: 33 men; mean age ± SD 43.6 ± 11.8 years; body mass index 29.7 ± 7.3 kg/m; and neck circumference 40.0 ± 3.4 cm. The overall prevalence of OSA was 38% (6 women and 13 men). Patients with OSA were older (49.8 ± 9.3 vs. 37.5 ± 10.8 years; P < 0.01) and had a higher body mass index (34.7 ± 8.1 vs. 26.2 ± 4.8 kg/m; P <0.01), neck circumference (41.2 ± 2.6 vs. 38.7 ± 3.6 cm; P < 0.01), and cylinder diopter (5.98 ± 1.94 vs. 4.05 ± 3.55 D; P = 0.045) compared with those without OSA. No significant association was found between OSA severity and ocular parameters and KCN grade. CONCLUSIONS: As measured by overnight home sleep apnea testing, OSA was 10 to 20 times more prevalent among patients with KCN than the rate reported for the general population. The rate lies between the prevalence estimated from sleep study data of self-reported diagnosis of OSA and the risk of developing OSA as determined by the Berlin Questionnaire.