Search

Purpose: To compare, between Alzheimer's disease (AD) patients and healthy individuals, corneal subbasal nerve plexus (CSNP) parameters and corneal sensitivities. Methods: Twenty-two patients who were followed up with Alzheimer's disease (Alzheimer's group) and 18 age- and gender-matched healthy individuals (control group) were included in this cross-sectional study. CSNP parameters, including nerve fiber length (NFL), nerve fiber density (NFD), and nerve branch density (NBD), were evaluated using in vivo confocal microscopy. Corneal sensitivity was evaluated using a Cochet-Bonnet esthesiometer. The results were compared between the two groups. Results: In the Alzheimer's group, NFL was 12.2 (2.4) mm/mm2, NFD was 12.5 [3.1] fibers/mm2, and NBD was 29.7 [9.37] branches/mm2. In the control group, NFL was 16.5 (2.0) mm/mm2, NFD was 25.0 [3.13] fibers/mm2, and NBD was 37.5 [10.9] branches/mm2. All three parameters were significantly lower in the Alzheimer's group compared to the control group (p < 0.001, p < 0.001, and p = 0.001, respectively). Similarly, corneal sensitivity was significantly lower in the Alzheimer's group (55.0 [5.0] mm) compared to the control group (60.0 [5.0] mm) (p < 0.001). Conclusion: We determined that, in AD, corneal sensitivity decreases significantly, in parallel with the decrease in corneal nerves. Changes in the corneal nerve plexus and a decrease in corneal sensitivity may be used in the early diagnosis and follow-up of AD. In addition, ocular surface problems secondary to these changes should also be kept in mind. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) remains the leading cause of blindness in the working-age population. Its progression causes gradual damage to corneal nerves, resulting in decreased corneal sensitivity (CS) and disruption of anterior-eye-surface homeostasis, which is clinically manifested by increased ocular discomfort and dry eye disease (DED). This study included 52 DR patients and 52 sex- and age-matched controls. Ocular Surface Disease Index (OSDI) survey, tear film-related parameters, CS, and in vivo corneal confocal microscopy (IVCM) of the subbasal plexus were performed. Furthermore, all patients underwent tear sampling for neurotrophin and cytokine analysis. OSDI scores were greater in DR patients than in controls (p = 0.00020). No differences in the Schirmer test score, noninvasive tear film-break-up time (NIBUT), tear meniscus or interferometry values, bulbar redness, severity of blepharitis or meibomian gland loss were found. In the DR group, both the CS (p < 0.001), and the scotopic pupil diameter (p = 0.00008) decreased. IVCM revealed reduced corneal nerve parameters in DR patients. The stage of DR was positively correlated with the OSDI (Rs = +0.51, 95% CI: + 0.35–+0.64, p < 0.001) and negatively correlated with IVCM corneal nerve parameters and scotopic pupillometry (Rs = −0.26, 95% CI: −0.44–−0.06, p = 0.0097). We found negative correlations between the OSDI and IVCM corneal innervation parameters. The DR group showed lower tear film-brain-derived neurotrophic factor (BDNF) levels (p = 0.0001) and no differences in nerve growth factor (NGF)-β, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-4, IL-5, IL-6, or IL-12 concentrations. Tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-γ levels were decreased among patients with DR. Corneal innervation defects have a direct impact on patients' subjective feelings. The evolution of DR appears to be associated with corneal nerve alterations, emphasizing the importance of IVCM. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet–Bonnet esthesiometer (Luneau®, Paris, France) and to quantitatively assess patient-reported discomfort during application. Methods: A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet–Bonnet esthesiometer's corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Results: Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0–58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups (P < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect (P = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect (P = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy (P < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine (P < 0.0001). Men reported experiencing more discomfort during instillation compared with women (P = 0.0168). Conclusions: Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort. [ABSTRACT FROM AUTHOR]

Neurotrophic keratitis or keratopathy (NK) is a degenerative corneal disease induced by impairment of the trigeminal nerve function. This condition may lead to persistent epithelial defects, corneal ulceration, and perforation. The diagnosis of NK requires a careful investigation of any ocular and systemic condition associated with the disease and ocular surface and corneal sensitivity examinations. In the past, several medical and surgical procedures were used to treat this condition with different clinical effectiveness. Cenegermin is a recombinant human nerve growth factor (rh-NGF) that supports corneal reinnervation. Different clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis. In this review, we report the literature on clinical results regarding the treatment of NK with cenegermin since its approval by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2017 and 2018, respectively.

AIM: To determine the corneal sensitivity recovery period after laser-assisted sub-epithelial keratectomy (LASEK) refractive surgery and investigate the effects of ablation depth on it. METHODS: In this study examinations were performed on 90 right eyes of 90 people (34 males and 56 females) with an age range of 20-35 and an average of 22.26±3.8 years old. A sensation of 5 corneal regions, including the center and 4 mid-peripheral regions, i.e., nasal, inferior, temporal, and superior, each at a distance of 2 mm from the center of the cornea were measured with a Cochet-Bonnet esthesiometer device in 3-time points including before LASEK, 1 and 3mo after the surgery, respectively. LASEK was performed on individuals with stabilized myopia of -1.00 to -7.00 diopters and astigmatism of less than 2.00 diopters. Furthermore, the individuals were divided into three groups regarding ablation depth. RESULTS: The highest level of corneal sensitivity before surgery was related to the center of the cornea (59.1±7.76), and the highest level of corneal sensitivity loss was also related to this region. The sensation of all measured corneal regions significantly reduced 1mo postoperatively and returned to their preoperative levels 3mo after surgery (mean of 5 corneal regions in levels of preoperation: 58.2±6.48, 1mo postoperation: 57.3±5.84, 3mo postoperation: 58.2±5.49; P

Objectives:To evaluate the corneal subbasal nerve morphology, corneal sensitivity, and anterior segment alterations in short-term silicone hydrogel contact lens (SiHCL) users by confocal microscopy.Materials and Methods:The study included 25 right eyes of 25 male volunteers aged 25-30 years who had never used SiHCLs before. ocular surface disease index (OSDI), tear break-up time, Schirmer test, tear meniscus area, strip meniscometry tube, corneal sensitivity, and corneal subbasal nerve morphology were evaluated before and after 1 month of CL use.Results:OSDI was 10.6±1.1 before CL use and 17.2±1.2 after 1 month of CL use (p0.05). Tear film break-up time was 7.1±0.4 s before and 6.2±0.3 s after CL use (p>0.05). The tear meniscus area was 0.026±0.002 mm2 before and 0.024±0.001 mm2 after 1 month of CL use (p>0.05). Stripmeniscometry tube results were 5.4±0.9 mm before and 4.9±0.8 mm after 1 month of CL use (p>0.05). Corneal sensitivity values were 3.2±0.4 mm before and 2.95±0.3 mm after 1 month of CL use (p>0.05). Dendritic cell density evaluated by confocal microscopy was 14.84±3.1 cells/mm2 before and 32.57±4.2 cells/mm2 after 1 month of CL use (p0.05). Subbasal nerve density was measured as 4726±310 pixels/frame before and 4570±272 pixels/frame after 1 month of CL use (p>0.05).Conclusion:After a month of SiHCL use, no significant changes were observed in tear secretion, corneal sensitivity, tear meniscus volume, subbasal corneal nerve density, reflectivity, or tortuosity, while a significant increase was found in OSDI and dendritic cell density.

Purpose: To analyse and quantify ocular surface parameters in patients with unilateral neurotrophic keratitis (NK) induced by trigeminal nerve injury post-neurosurgery. Methods: The study included 26 unilateral NK patients who had undergone neurosurgery, and 20 matched normal controls. Demographic and clinical characteristics of all participants were collected and analysed. Slit-lamp examination, Cochet–Bonnet aesthesiometry, Keratograph 5 M, and LipiView interferometer were performed on both eyes of 17 mild NK patients. For nine moderate/severe NK patients, sub-basal nerve density was measured by in vivo confocal microscopy. Results: Of the 26 patients, nine had acoustic neuroma, nine had trigeminal neuralgia, and eight had neoplasms. Facial nerve paralysis was observed in one of the 17 mild NK eyes (5.9%) and seven of the nine moderate/severe NK eyes (77.8%). Compared to contralateral and normal control eyes, 26 NK eyes showed significantly reduced sensitivity in five corneal regions (P < 0.05). Corneal sensitivity in moderate/severe NK eyes was significantly lower than in mild NK eyes (P < 0.05). Moderate/severe NK eyes had poor visual acuity, and their sub-basal nerve density was lower than that of the controls. The onset of the moderate/severe NK was from 0.5 to 24 months (median [Q1, Q3], 1 [0.5, 2.5] months) after neurosurgery. For the mild NK eyes, the number of total blinks, the first non-invasive tear breakup time (NITBUT) and average NITBUT were significantly lower than contralateral and normal control eyes (P < 0.05), and the number of partial blinks and partial blinking rate were significantly higher than the other two control groups (P < 0.05). Conclusions: Patients with NK induced by trigeminal nerve injury following neurosurgery had decreased corneal sensitivity to various degrees accompanied by increased partial blinks and shortened NITBUT. The severity of NK is related to the severity of the corneal sensory impairment. Facial nerve paralysis can worsen the clinical progression of NK. Trial registration Chinese Clinical Trial Registry (ChiCTR2100044068, Date of Registration: March 9, 2021). [ABSTRACT FROM AUTHOR]

To obtain a continuous range of clear vision for pseudophakic eyes, a design of intraocular lens (IOL) with extended depth of focus (EDoF) was proposed. The IOL was optimized with a multi-configuration approach based on a pseudophakic eye model and the optical performances of the designed IOL were analyzed. The modulation transfer function (MTF) values remain above 0.2 at 50 lp/mm for object distance ranging from 0.35 m to infinity in both photopic vision and mesopic vision over a field of 4°. The optical performances remain stable when the pupil diameter changes from 2.25 mm to 5 mm. Besides, the presented theoretical analyses show the designed IOL has good optical performances for polychromatic light and corneal asphericity. The above shows that the IOL exhibits an excellent ability for pseudophakic eyes to see the object in a continuous range of distance. [ABSTRACT FROM AUTHOR]

Neurotrophic keratopathy (NTK) is an orphan, polyetiological disease that has recently been identified more frequently. Drug-resistant stages of NTC often require urgent surgical treatment. Subsequently, such patients need to be done keratoplasty, the consequences may be unsatisfactory in the presence of a significant impairment of innervation.Purpose: to evaluate the effectiveness of lamellar anterior keratoplasty in patients with the outcome of stage II and III NTK.Material and methods. The study included 22 patients (22 eyes) aged 21 to 88 years. All patients were divided into two main groups. The first group consisted of 12 patients with NTC as a result of damage to the main stem of n.trigeminus and its branch n.ophthalmicus, the second group consisted of 10 patients — NTC as a result of toxic damage due to uncontrolled instillation of local anesthetics and eyedrops with preservatives. Before inclusion in the study, 14 patients underwent autoconjunctivoplasty for the treatment of drug-resistant NTK stage II and III, 8 — corneoscleral flap coating. All patients underwent lamellar anterior keratoplasty. The following parameters were assessed: maximally corrected visual acuity (MCVA) and coefficient of corneal sensitivity reduction in an approximate way before and after 1 day, 2 weeks, 1 and 3 months after surgery; tear film break- up time (Norn test) and Schirmer’s I.Results. In the second group an increase in the level of BCVA and a clear graft was observed in all patients, while in the first group, the level of BCVA worsened, and the graft was with reduced transparency. Significant difference between the examined and the fellow eye in the compared groups according to the tear film break-up time test was not detected. In the first group statistically significant decrease of tear production according to the results of the Schirmer’s test was identified. A weak correlation was found between corneal sensitivity and BCVA after surgery in group II.Conclusion. We have demonstrated the high efficiency of automated layered anterior keratoplasty in the outcomes of advanced stages of NTK of toxic etiology. In patients with NTC outcome as a result of stem injury, surgical treatment led to a satisfactory cosmetic result, but visual acuity did not change significantly.

Abstract Background Neurotrophic keratopathy (NK) is a rare, degenerative ocular disease characterized by reduction or loss of corneal sensitivity and development of non-healing corneal epithelial defects and ulcers. Cenegermin, a recombinant human nerve growth factor (rhNGF) eye drop solution, is the first drug approved for the treatment of NK. The aim of our study is to evaluate the long-term efficacy of this innovative topical treatment in patients with NK. Methods Retrospective, consecutive, observational case series study from a single-center setting (Department of Sense Organs, University Sapienza of Rome, Rome, Italy). 18 patients with diagnosis of stage 2 or 3 NK, treated with Cenegermin 20 mcg/ml eye drops were followed for up to 48 months. Recurrence of lesion during follow-up was evaluated at 12, 24, 36, and 48 months. In addition, corneal sensitivity, Schirmer tear test, and visual acuity (VA) were recorded at baseline, end of treatment, and at 12, 24, 36, and 48 months. Results Three patients experienced recurrence of persistent epithelial defects (PEDs) within 12 months and one patient experienced recurrence of a corneal ulcer within 36 months. Corneal sensitivity was significantly improved at all timepoints (P

Abstract 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.

Human intoxication after mercury exposure is a rare condition that can cause severe damage to the central nervous, respiratory, cardiovascular, renal, gastrointestinal, skin, and visual systems and represents a major public health concern. Ophthalmic involvement includes impaired function of the extraocular muscles and the eyelids, as well as structural changes in the ocular surface, lens, retina, and optic nerve causing a potential irreversible damage to the visual system. Although, there are many pathways for poisoning depending on the mercury form, it has been suggested that tissue distribution does not differ in experimental animals when administered as mercury vapor, organic mercury, or inorganic mercury. Additionally, visual function alterations regarding central visual acuity, color discrimination, contrast sensitivity, visual field and electroretinogram responses have also been described widely. Nevertheless, there is still controversy about whether visual manifestations occur secondary to brain damage or as a direct affectation, and which ocular structure is primarily affected. Despite the use of some imaging techniques such as in vivo confocal microscopy of the cornea, optical coherence tomography (OCT) of the retina and optic nerve, and functional tests such as electroretinography has helped to solve in part this debate, further studies incorporating other imaging modalities such as autofluorescence, OCT angiography or adaptive optics retinal imaging are needed. This review aims to summarize the published structural and functional alterations found in the visual system of patients suffering from mercury intoxication.

Objectives: To evaluate the corneal subbasal nerve morphology, corneal sensitivity, and anterior segment alterations in short-term silicone hydrogel contact lens (SiHCL) users by confocal microscopy. Materials and Methods: The study included 25 right eyes of 25 male volunteers aged 25-30 years who had never used SiHCLs before. ocular surface disease index (OSDI), tear break-up time, Schirmer test, tear meniscus area, strip meniscometry tube, corneal sensitivity, and corneal subbasal nerve morphology were evaluated before and after 1 month of CL use. Results: OSDI was 10.6±1.1 before CL use and 17.2±1.2 after 1 month of CL use (p<0.01). Schirmer test distance was 16.3±2.3 mm before and 14.3±1.9 mm after 1 month of CL use (p>0.05). Tear film break-up time was 7.1±0.4 s before and 6.2±0.3 s after CL use (p>0.05). The tear meniscus area was 0.026±0.002 mm² before and 0.024±0.001 mm² after 1 month of CL use (p>0.05). Strip meniscometry tube results were 5.4±0.9 mm before and 4.9±0.8 mm after 1 month of CL use (p>0.05). Corneal sensitivity values were 3.2±0.4 mm before and 2.95±0.3 mm after 1 month of CL use (p>0.05). Dendritic cell density evaluated by confocal microscopy was 14.84±3.1 cells/mm² before and 32.57±4.2 cells/mm² after 1 month of CL use (p<0.01). Subbasal nerve tortuosity was 0.92±0.2 before and 1.03±0.2 after 1 month of CL use (p>0.05). Subbasal nerve density was measured as 4726±310 pixels/frame before and 4570±272 pixels/frame after 1 month of CL use (p>0.05). Conclusion: After a month of SiHCL use, no significant changes were observed in tear secretion, corneal sensitivity, tear meniscus volume, subbasal corneal nerve density, reflectivity, or tortuosity, while a significant increase was found in OSDI and dendritic cell density. [ABSTRACT FROM AUTHOR]

Purpose: Primarily, to evaluate the repeatability and reproducibility of the new non-contact esthesiometer (NCE) in healthy subjects. Secondarily, the corneal sensitivity threshold measurements of the NCE were compared with those of the Cochet-Bonnet esthesiometer (CBE)., Design: Assessment reliability study., Methods: Two examiners measured bilateral corneal sensitivity thresholds by NCE and CBE. Triple NCE measurements were performed per eye at all five levels, whereas single CBE measurements were performed per eye. When appropriate, NCE (mBar) and CBE (mm) measurements were converted to millinewtons (mN) for direct comparison between devices. The NCE measurement variations were calculated with the intra-class correlation coefficients (ICC) for the primary objective. For the secondary objective, Bland-Altman plots with 95% limits of agreement (95%-LoA) and Spearman's rank correlation coefficients were used to evaluate the level of agreement and linear relationship between the corneal sensitivity thresholds obtained with both devices. Generalized estimating equation models were used to account for the inter-eye correlation of the same study participant., Results: Fifty subjects (100 eyes) aged 29 years (median) were included. There were no statistically significant differences in the pressure measured by both observers at each NCE level (all p > 0.05). There was a high intra-observer and inter-observer repeatability of the NCE measurements (ICC > 0.90) and a strong linear correlation (rho > 0.7) at each NCE level. The difference between the mean corneal sensitivity thresholds (mN) measured with the NCE (0.052 ± 0.021 mN) and CBE (0.046 ± 0.005 mN) was statistically significant (p = 0.001). Bland-Altman analysis revealed a differential bias of +0.00578 mN (95%-LoA -0.03677 - +0.04833 mN) between threshold measurements., Conclusions: The NCE provides reliable user-independent corneal sensitivity measurements. The NCE and CBE do not yield similar values. Thus, both devices cannot be used interchangeably., Competing Interests: Declaration of competing interest Raul E. Ruiz-Lozano: I have nothing to declare, Manuel E. Quiroga-Garza: I have nothing to declare, Eugenia M. Ramos-Dávila: I have nothing to declare, Jezreel Pantaleón García: I have nothing to declare, Ali Khodor: I have nothing to declare, Seitaro Komai: I have nothing to declare, Luis A. Rodriguez-Gutierrez: I have nothing to declare, Symon Ma: I have nothing to declare, Hazem M. Mousa: I have nothing to declare, Robby Mattes: I have nothing to declare, Sandra S. Stinnett: I have nothing to declare, Alfonso L. Sabater: Ocubio, Tissuecor, Brill Pharma, Abbvie, GlaxoSmithKline, Victor L. Perez: Claris Biotherapeutics, Dompé, Kala, Nicox, Novartis, Thea, Trefoil, Brill Pharma, BRIM Biotechnology. National Institutes of Health (U01 EY034687 and P30 EY005722) and Research to Prevent Blindness Unrestricted Grant to Duke University., (Copyright © 2024. Published by Elsevier Inc.)

Clinical Relevance: Knowing the changes in corneal sensitivity according to age and gender is important for the correct evaluation of pathologies., Background: The aim of this work was to analyse variability of corneal sensitivity according to age and gender in the healthy population in Turkey., Methods: Healthy volunteers between the ages of 20 and 84, who applied to outpatient clinic due to routine examination, were included. Exclusion criteria were any ocular diseases other than refractive error, any systemic disease, contact lens use, chronic ocular and systemic drug use, and previous ocular surgery. Central and 4 quadrants (superior, inferior, nasal, temporal) corneal sensitivity measurements were performed with a Cochet-Bonnet esthesiometer (Luneau Ophthalmology, France). The patients were divided into 5 groups according to their ages (Group 1:20-29, Group 2:30-39, Group 3:40-49, Group 4:50-59, Group 5 ≥ 60). The data were evaluated in terms of groups and gender., Results: The right eyes of 324 volunteers were included. The mean age was 44.31 ± 15.65 (20-84) and the female/male ratio was 165/159. The mean central, superior, inferior, nasal, and temporal sensitivities were 50.15 ± 9.7,48.62 ± 10.3,48.59 ± 10.3,47.73 ± 10.2,47.71 ± 10.3 mm, respectively. Sensitivities in all quadrants decreased significantly depending on age ( p  = 0.001 for all, central, superior, inferior, nasal and temporal correlation coefficients, r  = -0.783, -0.791, -0.789, -0.760, -0.775, respectively). The decrease accelerated in Group 4 and 5. Gender-related changes were detected as significant in central and temporal quadrants ( p  = 0.038, p  = 0.019). When sensitivity according to gender was evaluated within each decade, significant difference was detected in Group 2 and 4 ( p  < 0.05)., Conclusion: Corneal sensitivity decreases with age, most significantly in 5 th and 6 th decades. Sensitivity differs between genders in central and temporal quadrants. Geographic location, gender, and ethnicity may affect sensitivity values. The present study defines normal values in aTurkish population and may guide the evaluation of pathologies that impair corneal sensitivity.

PURPOSE: The purpose of the study was to evaluate the corneal sensitivity and its quadrature variability in patients with diabetic neuropathy (DN) diagnosed with electromyography and to compare these results with age- and sex-matched healthy individuals. METHODS: The left eyes of 32 patients who applied for refraction or fundus examination and had a diagnosis of DN by electromyography in their medical history were included in this study. Corneal sensitivity was evaluated using the Cochet–Bonnet esthesiometer (Luneau, Paris) in five zones: central, nasal, superior, temporal, and inferior. The measurements of the patients were compared with the measurements of 32 age- and sex-matched healthy volunteers. Furthermore, the measurements of five corneal zones were compared with each other, and the level of correlation was investigated in each group. RESULTS: The central corneal sensitivity values were measured as 4.12 ± 1.04 (mm) and 5.92 ± 0.14 (mm) (P < 0.001). While the sensitivity values at the superior, inferior, nasal, and temporal quadrants were detected as 5.85 ± 0.21, 5.85 ± 0.26, 5.94 ± 0.13, 5.93 ± 0.13, and 5.92 ± 0.14 (mm) in the control group, it was measured as 3.67 ± 0.66, 3.67 ± 0.62, 3.67 ± 0.62, and 3.89 ± 0.73 (mm) in the DN group, respectively. The corneal sensitivity values were all found to be significantly lower in the DN group (P < 0.001 for all parameters) at all quadrants as well as the central cornea. Furthermore, a moderate positive correlation between all five zones in the control group and a very strong positive correlation in the DN group were found in terms of the corneal quadrature sensitivity. CONCLUSION: The current study revealed a significant reduction in corneal sensitivity in patients with DN. In both the control group and DN group, all corneal zones showed positive correlations which show the consistency of the measurement in different quadratures. Evaluating corneal sensitivity with a Cochet–Bonnet esthesiometer might serve as a useful screening tool in detecting neuropathy development. By taking the necessary precautions, further damage can be prevented. [ABSTRACT FROM AUTHOR]

An objective method of early identification of people at risk of chemotherapy-induced peripheral neuropathy is needed to minimize long-term toxicity and maximize dose intensity. The aims of the study were to observe corneal nerve microstructure and corneal sensitivity changes and peripheral neuropathy in patients receiving oxaliplatin, and to determine its association with corneal parameters at different stages of treatment and assess utility as non-invasive markers to detect and monitor peripheral neuropathy. Twenty-three patients scheduled to receive oxaliplatin chemotherapy with intravenous 5-FU for gastro-intestinal cancer were recruited and followed up with for 12 months. Ocular examinations including corneal and retinal evaluations, alongside peripheral neuropathy assessment, were performed. The corneal nerve density did not show significant change after chemotherapy when measured with a widely used semi-automated program or an automated analysis technique. Macula and optic nerve function did not change during or after oxaliplatin chemotherapy. However, the corneal nerve density modestly correlated with clinical peripheral neuropathy after 20 weeks of chemotherapy (r = 0.61, p = 0.01) when peripheral neuropathy is typical most profound, and corneal nerve sensitivity correlated with neuropathy at 12 (r = 0.55, p = 0.01) and 20 weeks (r = 0.64, p = 0.006). In conclusion, corneal changes detected on confocal microscopy show moderate association with peripheral neuropathy, indicating their potential to identify the development of oxaliplatin-induced peripheral neuropathy. However, further studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Impairment in trigeminal nerve function causes a loss of corneal sensation and can lead to neurotrophic keratitis (NK). This gradual deterioration in the surface integrity of the cornea predisposes to the development of ulcers and may even progress to perforation, posing a risk for profound vision loss. Many common ophthalmic and systemic conditions, such as herpetic infections, ocular surgeries, neurosurgical procedures, multiple sclerosis and diabetes, can elicit NK by injuring the trigeminal nerve. Disease progression can occur rapidly and without symptoms, therefore, detecting NK early is critical. Management aims to halt continuing corneal damage and promote epithelial cell healing and nerve fibre regeneration. Novel treatment options show promise in restoring corneal sensitivity by re-establishing innervation, targeting the fundamental source of NK. [ABSTRACT FROM AUTHOR]

Purpose: To describe and evaluate relevant physical properties of the Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) for ocular surface sensitivity measurement. Methods: Characteristics of Liquid Jet (LJ) droplets (consisting of isotonic saline solution) were analysed: vertical and horizontal displacement and speed of LJ droplets were recorded with the aid of the High Speed Photron FASTCAM NOVA S6 camera (stimulus duration: 40 ms). Stimulus mass was assessed for 20 sets of 10 LJs with aid of a microbalance (pressure range of 100–1500 mbar). Results: Because continuous flow LJ disintegrated into droplets in the lower pressure range (<700 mbar), pulsed stimuli were applied in order to obtain similar stimulus characteristics across the applied pressure range. For all measurements, very little variability was observed. Vertical and horizontal displacement did not exceed 0.13 mm in either direction. The mass per shot showed an unexpected cubic dependency on pressure. Up to approximately 700 mbar, LJ speed showed an almost linear relationship. For the pressure range of >700–1500 mbar, variability increased and speed decreased compared to the expected in a linear manner. However, this may be caused by the difficulty of identifying pattern changes of LJ droplets from one high speed image frame to the next with increasing stimulus speed, when determining LJ speed via pixel count. Conclusions: Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity was shown to deliver fine droplets with a pulsed stimulus mode, in a repeatable manner with precise localisation to the ocular surface. Very little variability was observed in LJ speed and mass for the typical pressure range required for clinical sensitivity measurements. [ABSTRACT FROM AUTHOR]

Abstract Background Traumatic dislocation of laser-assisted in situ keratomileusis (LASIK) corneal flaps is an uncommon postoperative complication that could occur any time after LASIK, and could be visually devastating. We evaluated the visual outcomes, corneal sensation, tear function, and dry eye questionnaire results of patients with traumatic dislocation of LASIK flaps, including one LASIK flap amputation. Methods This is a retrospective case series. Seven patients who were diagnosed with traumatic displacement of the LASIK flap and underwent flap replacement surgery between August 2014 and January 2019 were included.Patient’s visual acuity, refraction, corneal sensitivity, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH), and ocular surface disease index (OSDI) results were evaluated. Results The patients’ mean age was 35.86 ± 5.84 years, and 42.9 % (3/7) were male. The mean duration from LASIK to trauma was 8.86 ± 2.48 years.The mean preoperative and postoperative six-month corrected distance visual acuity (CDVA) were 0.55 ± 0.34 and 0.02 ± 0.03, respectively. The mean spherical equivalent and astigmatism at six months postoperatively was − 1.0 ± 0.95 D and − 0.5 ± 0.25 D, respectively. The corneal flap was clear and well-positioned at the final follow-up (mean: 28.57 ± 6.9 months). 85.71 % (6/7) of the patients showed worse corneal sensation in the injured eye. Interocular OSDI discrepancy was less in those whose last visit was more than 30 months after the trauma. Conclusions Postoperative CDVAat six months was improved, and the refractive data also showed some improvement. The corneal nerve and tear function recovery peaked before 30 months, while the OSDI continued to show a strong trend of improvement beyond 30 months.

Purpose: The aim of this study was to investigate the association between alterations in corneal subbasal nerve plexus and tactile corneal sensitivity in patients with Fuchs' endothelial corneal dystrophy (FECD). Methods: This retrospective, cross-sectional study included 24 (10 M/14 F) patients with FECD and 25 age- and sex-matched (10 M/15 F) healthy subjects as controls. Subjects with FECD were classified as having early (grades 1 and 2) and late (grades 3 and 4) disease. All subjects underwent central corneal tactile sensitivity measurements with the Cochet–Bonnet esthesiometer (Luneau Ophthalmologie, Chartres, France) and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). Association between corneal nerve plexus density and corneal sensitivity alterations were evaluated using the Mann–Whitney U test and the Spearman correlation test. Results: Compared to healthy subjects (mean age = 60.4 ± 7.5 years), patients with FECD (mean age = 60.6 ± 8.0 years) had worse central corneal sensitivity scores (5.9 ± 0.1 cm vs. 4.2 ± 0.8 cm; P < 0.001), reduced corneal nerve fibers (3.4 ± 1.3 nerves/frame vs. 5.0 ± 0.9 nerves/frame; P < 0.001) and lower corneal subbasal nerve plexus densities (2229.4 ± 364.3 μm/mm2 vs. 1901.6 ± 486.8 μm/mm2; P = 0.050). Patients with late stage FECD demonstrated lower subbasal nerve densities as compared to those with early disease (2204.3 ± 313.1 μm/mm2 (range = 1523–2552 μm/mm2); 1397.1 ± 227.4 μm/mm2 (range = 1120-1834 μm/mm2); P < 0.001). In the FECD group, subbasal nerve density was found to be directly correlated with corneal sensitivity scores (r = 0.457, P = 0.025). Conclusion: Progressive loss of the corneal subbasal nerve plexus appears to be a consistent feature of FECD. Reduction of the corneal nerve plexus parallels the decrease in corneal sensitivity in this patient population.

Purpose: To measure the corneal sensitivity in patients with multiple sclerosis (MS), to compare it with normal values and to study its correlation with different disease characteristics. Methods: Corneal sensitivity of 28 MS patients was compared to corneal sensitivity of 28 age- and gender-matched normal controls. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer and was correlated to the duration, type and severity indexes of the disease. Results: Corneal sensitivity was comparable between both groups (P = 0.79). No statistically significant correlation was found between corneal sensitivity and the duration of MS (P = 0.55) nor the severity indexes of MS (expanded disability status scale [EDSS] P = 0.52, global multiple sclerosis severity score [MSSS] P = 0.64). Following subgroup analysis, only the primary progressive (PPMS) form of MS had a reduced corneal sensitivity with P = 0.023, while remittent-recurrent (RRMS), secondary progressive (SPMS), and clinically isolated (CIS) forms of MS did not have any reduction in the corneal sensitivity. “ROC curve analysis” showed an area under the curve of 0.48. Conclusion: In the exception of PPMS subtype, MS patients have similar corneal sensitivity in comparison to controls. Cochet-Bonnet esthesiometer does not seem to be a good diagnostic tool or a disease severity marker for patients with MS.

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. [ABSTRACT FROM AUTHOR]

Background: Neurotrophic keratopathy (NK) is a rare, degenerative ocular disease characterized by reduction or loss of corneal sensitivity and development of non-healing corneal epithelial defects and ulcers. Cenegermin, a recombinant human nerve growth factor (rhNGF) eye drop solution, is the first drug approved for the treatment of NK. The aim of our study is to evaluate the long-term efficacy of this innovative topical treatment in patients with NK.Methods: Retrospective, consecutive, observational case series study from a single-center setting (Department of Sense Organs, University Sapienza of Rome, Rome, Italy). 18 patients with diagnosis of stage 2 or 3 NK, treated with Cenegermin 20 mcg/ml eye drops were followed for up to 48 months. Recurrence of lesion during follow-up was evaluated at 12, 24, 36, and 48 months. In addition, corneal sensitivity, Schirmer tear test, and visual acuity (VA) were recorded at baseline, end of treatment, and at 12, 24, 36, and 48 months.Results: Three patients experienced recurrence of persistent epithelial defects (PEDs) within 12 months and one patient experienced recurrence of a corneal ulcer within 36 months. Corneal sensitivity was significantly improved at all timepoints (P < 0.05). Significant improvements in visual acuity and tear production were seen at the completion of treatment as well as at 12, 24, and 36 months (P < 0.05) when compared to baseline.Conclusions: A single 8-week treatment regimen of Cenegermin eye drops has clinical efficacy that can persist for up to 48 months. The long-term clinical utility of treatment with Cenegermin for NK was demonstrated through the low rate of lesion recurrence along with improvements in corneal sensitivity and tear production. [ABSTRACT FROM AUTHOR]

Background: The presence of diabetic keratopathy associated with diabetic corneal neuropathy should be taken into account in the management of corneal inflammation in patients with diabetes mellitus. Purpose: To determine the impact of adjunctive topical autologous serum eye drops on delayed healing of bacterial corneal ulcers in patients with type 1 diabetes mellitus (DM1). Material and Methods: We retrospectively reviewed the results of observing 19 DM1 patients (19 eyes) with bacterial corneal ulcers who exhibited delayed healing of corneal ulceration and whose corneal smears and scrapings taken one week after initiation of treatment were bacteriologically negative. Patients had a routine eye examination (visual acuity, tonometry, and slit-lamp biomicroscopy of anterior and posterior eye segments), bacteriological studies, fluorescein dye test, anterior eye OCT and non-contact corneal esthesiometry. Patients of the control group (9 individuals) continued receiving only background therapy (topical antiseptics, antioxidants, repairing agents, artificial tears, and mydriatics and systemic anti-inflammatory agents), whereas patients of the main group began receiving autologous serum eye drops in addition to background therapy of topical antiseptics, mydriatics and systemic anti-inflammatory agents. Clinical picture data for day 1 (visit 1, before administering the treatment) and days 7 (when corneal samples and scrapings were re-taken), 14 (when bacteriology results became available and main group patients were additionally administered autologous serum), 17, 21 and 24 were analyzed. Results: In DM1 patients with delayed healing of bacterial corneal ulcers, the use of adjunctive autologous serum eye drops after eradication of the offending microorganisms resulted in reductions in precorneal injection and size and depth of the ulcer defect and complete resolution of corneal infiltration and edema of the corneal tissue surrounding the ulcer as early as day 3, and recovery of all patients and a 32.6% improvement in corneal sensitivity on day 10. Conclusion: Using adjunctive topical autologous serum eye drops after eradication of the offending microorganisms was found to be efficacious in the comprehensive treatment of delayed healing of bacterial corneal ulcers in patients with DM1.

Abstract Background To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy. Methods This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups. Results 29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p

Purpose: Diabetic peripheral neuropathy can be detected using non-invasive in vivo confocal microscopy of the cornea (IVCM) and such abnormalities may precede the development of clinical neuropathy. The current study aimed to assess any progression or remission of corneal and peripheral neuropathy in patients with type 2 diabetes undergoing bariatric surgery., Methods: People with known type 2 diabetes for at least five years and listed for bariatric surgery were recruited. Participants were assessed before, and 12, 26, and 52 weeks following bariatric surgery. IVCM and corneal sensitivity measurements were performed. A modified total neuropathy score (mTNS) was obtained from neuropathy questionnaire, clinical assessment and biothesiometry., Results: Twenty-nine participants (M:F, 11:18) with mean BMI of 44.7 ± 6.4 kg/m 2 , and 11 ± 7.6 years duration of diabetes, were assessed. Corneal sub-basal nerve fibre length (CNFL), displayed an increase from a baseline mean of 12.20 ± 1.00 to 17.48 ± 0.92 mm/mm 2 at 52 weeks (p < 0.0001). Corneal sensitivity threshold displayed a decrease over time, thus corneal sensitivity improved, falling from a mean of 1.11 ±0 .15 to 0.62 ± 0.11 (mBAR) (p < 0.0001). Clinical neuropathy scores demonstrated significant improvements from baseline, displaying a decrease in average mTNS score from 3.29 ± 0.68 to 0.76 ± 0.30 (p < 0.0001). A significant inverse relationship was shown between CNFL and sensitivity (β coefficient = -0.047, p < 0.001), and CNFL and mTNS (β coefficient = -0.178, p < 0.001)., Conclusion: Bariatric surgery led to an improvement in metabolic control of diabetes and weight loss, along with improvement in corneal nerve microstructure, corneal sensitivity, and neuropathic symptoms, suggesting a reversal of both small and large fibre neuropathy., Competing Interests: Declaration of competing interest Jonathan D Oakley is the creator of DeepNerve software. All the authors have no conflicts of interest to declare related to this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the corneal sensitivity of black diabetic patients and identify factors associated with changes in corneal sensitivity., Methodology: We conducted a cross-sectional comparative case-control study at the National Obesity Center of the Yaounde Central Hospital and the Djoungolo District Hospital from March 1 to July 31, 2022. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer in all diabetic patients over 18 years of age, matched for age and sex to a clinically healthy control population. Data were analyzed using SPSS version 23.0 software. A P-value of less than 5% was considered significant., Results: A total of 111 diabetic and 111 non-diabetic patients participated in the study. The mean age was 53.46±12.74 years for diabetics and 52.85±11.77 years for non-diabetics (P=0.901). The mean duration of diabetes was 6.4±5.30 years. Corneal sensitivity in diabetics was lower (44.56±9.59mm) compared to non-diabetics (53.59±6.30mm) with a statistically significant difference (P=0.000). Factors associated with decrease in corneal sensitivity in diabetics were duration of diabetes and poor glycemic control., Conclusion: Decrease in corneal sensitivity related to diabetes is a complication to be systematically screened for during the ophthalmologic follow-up of diabetic patients., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose: To quantify the severity and location of corneal neovascularization (cNV) and its impact on the visual acuity and corneal sensitivity in a cohort of the patients referred to a specialist cornea clinic and also to describe the etiology of cNV in the cohort.Methods: We retrospectively evaluated the charts of 13,493 subjects referred to the San Raffaele Cornea Unit between January 2004 and December 2018 to search for cNV diagnosis. The corneal neovascularization severity was measured in the quadrants (range: 1–4) and location was defined as superficial, deep, or both. Best spectacle corrected visual acuity (BSCVA) was measured in logMar. We used the multiple regression analysis to identify the independent predictors of logMAR, after adjusting for age, gender, keratoconus, herpes keratitis, penetrating keratoplasty, trauma, and cataract surgery.Results: Corneal neovascularization was diagnosed in 10.4% of the patients analyzed. The most prevalent etiology of cNV in our population was non-infectious corneal dystrophies/degenerations followed by herpes simplex virus infection. cNV affected OD, OS, or both eyes in 35.6, 40.2, and 24.2 of cases, respectively. Mean BSCVA (SD) was 0.59 (0.76), 0.74 (0.94), and 1.24 (1.08) in cNV one, two, and three or four of the quadrant groups. Superficial, deep, or mixed cNV occurred in 1,029, 348, and 205 eyes. Severe cNV (three or four of the quadrants) was a significant predictor of low visual acuity (p < 0.001) and reduced corneal sensitivity (p < 0.05). cNV location and its severity were associated (p < 0.05). In addition, corneal anesthesia was associated with lower BSCVA (p < 0.001).Conclusion: Severe and deep cNV are associated with the reduced visual acuity and corneal sensitivity. Our data strongly support the relevance of appropriate follow-up as cNV is a major risk factor for graft rejection.

Purpose: To measure the corneal sensitivity in patients with multiple sclerosis (MS), to compare it with normal values and to study its correlation with different disease characteristics.Methods: Corneal sensitivity of 28 MS patients was compared to corneal sensitivity of 28 age- and gender-matched normal controls. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer and was correlated to the duration, type and severity indexes of the disease.Results: Corneal sensitivity was comparable between both groups (P = 0.79). No statistically significant correlation was found between corneal sensitivity and the duration of MS (P = 0.55) nor the severity indexes of MS (expanded disability status scale [EDSS] P = 0.52, global multiple sclerosis severity score [MSSS] P = 0.64). Following subgroup analysis, only the primary progressive (PPMS) form of MS had a reduced corneal sensitivity with P = 0.023, while remittent-recurrent (RRMS), secondary progressive (SPMS), and clinically isolated (CIS) forms of MS did not have any reduction in the corneal sensitivity. "ROC curve analysis" showed an area under the curve of 0.48.Conclusion: In the exception of PPMS subtype, MS patients have similar corneal sensitivity in comparison to controls. Cochet-Bonnet esthesiometer does not seem to be a good diagnostic tool or a disease severity marker for patients with MS. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the effect of chalazion excision on corneal aberrations and corneal densitometry. Methods: Thirty-six patients with a chalazion in 1 eyelid and 40 healthy subjects were included in the study. Corneal aberration parameters of total root mean square (RMS), RMS high-order aberration (HOA), horizontal trefoil, oblique trefoil, horizontal coma, vertical coma, and spherical aberration values were measured using Scheimpflug corneal topography (Pentacam HR; Oculus Optikgeräte GmbH, Wetzler, Germany). Corneal densitometry values measured from 4 regions of the cornea (0-2, 2-6, 6-10, and 10-12 mm) and 4 corneal depths (anterior, central, posterior, and total) were recorded. Preoperative measurements of the patients (Group 1), postoperative first-month measurements (Group 2), and control group (Group 3) measurements were compared. Results: The total RMS measurement was 1.64±0.48 µm in Group 1, 1.35±0.32 µm in Group 2, and 1.17±0.38 µm in Group 3 (Group 1-2: p=0.007, Group 1-3: p<0.001, Group 2-3: p=0.173). The mean spherical aberration value was 0.183±0.057 µm in Group 1, 0.157±0.048 µm in Group 2, and 0.144±0.050 µm in Group 3 (Group 1-2: p=0.104, Group 1-3: p=0.004, Group 2-3: p=0.781). The total corneal densitometric measurement was 15.95±1.80 gray scale units (GSU) in Group 1, 14.76±1.76 GSU in Group 2, and 14.33±1.49 GSU in Group 3 (Group 1-2: p=0.01, Group 1-3: p<0.001, Group 2-3: p=0.804). Conclusion: It was observed that some corneal aberration and corneal densitometry values were higher in patients with a chalazion compared with those of healthy individuals, and there was a decrease in corneal aberration and densitometry values after surgical excision. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate clinical and in vivo confocal microscopy (IVCM) findings of a patient who developed multiple unilateral subepithelial stromal opacities following conjunctivitis that developed during a COVID-19 infection. Methods: A 22-year-old female presented to our clinic with blurred right vision. The history revealed that she had experienced a COVID-19 infection one month ago. Redness and stinging of the right eye had started at the same time and she had been prescribed topical antibiotic drops and ointments. The redness in the right eye had decreased but blurred vision had then developed. Results: Slit lamp examination revealed a normal left eye. Several tiny subepithelial infiltrates without fluorescein staining of the cornea were present in the right eye. The anterior chamber, lens and fundus were bilaterally normal. IVCM revealed irregular corneal epithelial cells with bright borders in addition to scattered inflammatory cells and cell debris in the right eye. There were activated dendritic cells in the subbasal epithelial area with a significant decrease in the subbasal corneal nerve plexus. Clusters of highly reflective cells with an irregular shape were seen in the anterior corneal stroma together with foci of activated keratocytes. The corneal endothelial cell layer was normal. The left eye IVCM findings were all within normal limits. The right eye also showed decreased corneal sensitivity compared to the left. Conclusions: The possible role of corneal infiltrates as a trigger for COVID-19 could be explained with an immune-mediated mechanism. SARS-CoV-2 can result in decreased corneal sensitivity through corneal nerve involvement. The clinical results of this effect need to be evaluated in larger series. [ABSTRACT FROM AUTHOR]

Abstract Laser-assisted in situ keratomileusis (LASIK) is the most commonly performed laser refractive surgical technique worldwide for the treatment of myopia and myopic astigmatism. In recent years, small incision lenticule extraction (SMILE) has emerged as a promising alternative to LASIK, requiring only a single femtosecond laser to create an intrastromal lenticule, which is then removed via a small incision. The technique obviates the need for a corneal flap. A number of published studies have compared the two techniques in terms of visual, refractive and ocular surface outcomes. This review compares the clinical outcomes between LASIK and SMILE in treating myopia and myopic astigmatism based on studies published in the last 5 years. Twenty-two studies were included, all of which were observational in nature. Results suggest that the two techniques have comparable visual outcomes in terms of safety, efficacy and predictability, although recovery in visual acuity may be slower in SMILE-treated than LASIK-treated eyes. SMILE is found to result in less severe postoperative dry eye symptoms and faster recovery of corneal sensitivity than LASIK. It is important to note, however, that the SMILE technique is limited by the lack of a cyclotorsion-compensation system and option for customized treatment profile. The heterogeneity of results in this review may be attributable to the use of different LASIK platforms in different studies. Few studies compared the outcomes regarding severity of myopia. Future prospective randomized controlled trials with a larger sample size and longer follow-up period will be highly beneficial for progress in this field.

Neuropathic ocular pain is a frequent occurrence in medium to severe dry eye disease (DED). Only palliative treatments, such as lubricants and anti-inflammatory drugs, are available to alleviate patients’ discomfort. Anesthetic drugs are not indicated, because they may interfere with the neural feedback between the cornea and the lacrimal gland, impairing tear production and lacrimation. Gabapentin (GBT) is a structural analog of gamma-amino butyric acid that has been used by systemic administration to provide pain relief in glaucomatous patients. We have already shown in a rabbit model system that its topic administration as eye drops has anti-inflammatory properties. We now present data on rabbits’ eyes showing that indeed GBT given topically as eye drops has analgesic but not anesthetic effects. Therefore, opposite to an anesthetic drug such as oxybuprocaine, GBT does not decrease lacrimation, but–unexpectedly–even stimulates it, apparently through the upregulation of acetylcholine and norepinephrine, and by induction of aquaporin 5 (AQP5) expression in the lacrimal gland. Moreover, data obtained in vitro on a primary human corneal epithelial cell line also show direct induction of AQP5 by GBT. This suggests that corneal cells might also contribute to the lacrimal stimulation promoted by GBT and participate with lacrimal glands in the restoration of the tear film, thus reducing friction on the ocular surface, which is a known trigger of ocular pain. In conclusion, GBT is endowed with analgesic, anti-inflammatory and secretagogue properties, all useful to treat neuropathic pain of the ocular surface, especially in case of DED.

Purpose: The aim of this study was to investigate the association between alterations in corneal subbasal nerve plexus and tactile corneal sensitivity in patients with Fuchs' endothelial corneal dystrophy (FECD).Methods: This retrospective, cross-sectional study included 24 (10 M/14 F) patients with FECD and 25 age- and sex-matched (10 M/15 F) healthy subjects as controls. Subjects with FECD were classified as having early (grades 1 and 2) and late (grades 3 and 4) disease. All subjects underwent central corneal tactile sensitivity measurements with the Cochet-Bonnet esthesiometer (Luneau Ophthalmologie, Chartres, France) and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). Association between corneal nerve plexus density and corneal sensitivity alterations were evaluated using the Mann-Whitney U test and the Spearman correlation test.Results: Compared to healthy subjects (mean age = 60.4 ± 7.5 years), patients with FECD (mean age = 60.6 ± 8.0 years) had worse central corneal sensitivity scores (5.9 ± 0.1 cm vs. 4.2 ± 0.8 cm; P < 0.001), reduced corneal nerve fibers (3.4 ± 1.3 nerves/frame vs. 5.0 ± 0.9 nerves/frame; P < 0.001) and lower corneal subbasal nerve plexus densities (2229.4 ± 364.3 μm/mm2 vs. 1901.6 ± 486.8 μm/mm2; P = 0.050). Patients with late stage FECD demonstrated lower subbasal nerve densities as compared to those with early disease (2204.3 ± 313.1 μm/mm2 (range = 1523-2552 μm/mm2); 1397.1 ± 227.4 μm/mm2 (range = 1120-1834 μm/mm2); P < 0.001). In the FECD group, subbasal nerve density was found to be directly correlated with corneal sensitivity scores (r = 0.457, P = 0.025).Conclusion: Progressive loss of the corneal subbasal nerve plexus appears to be a consistent feature of FECD. Reduction of the corneal nerve plexus parallels the decrease in corneal sensitivity in this patient population. [ABSTRACT FROM AUTHOR]

Neuropathic ocular pain is a frequent occurrence in medium to severe dry eye disease (DED). Only palliative treatments, such as lubricants and anti-inflammatory drugs, are available to alleviate patients' discomfort. Anesthetic drugs are not indicated, because they may interfere with the neural feedback between the cornea and the lacrimal gland, impairing tear production and lacrimation. Gabapentin (GBT) is a structural analog of gamma-amino butyric acid that has been used by systemic administration to provide pain relief in glaucomatous patients. We have already shown in a rabbit model system that its topic administration as eye drops has anti-inflammatory properties. We now present data on rabbits' eyes showing that indeed GBT given topically as eye drops has analgesic but not anesthetic effects. Therefore, opposite to an anesthetic drug such as oxybuprocaine, GBT does not decrease lacrimation, but–unexpectedly–even stimulates it, apparently through the upregulation of acetylcholine and norepinephrine, and by induction of aquaporin 5 (AQP5) expression in the lacrimal gland. Moreover, data obtained in vitro on a primary human corneal epithelial cell line also show direct induction of AQP5 by GBT. This suggests that corneal cells might also contribute to the lacrimal stimulation promoted by GBT and participate with lacrimal glands in the restoration of the tear film, thus reducing friction on the ocular surface, which is a known trigger of ocular pain. In conclusion, GBT is endowed with analgesic, anti-inflammatory and secretagogue properties, all useful to treat neuropathic pain of the ocular surface, especially in case of DED. [ABSTRACT FROM AUTHOR]

The emergence of SMILE in the last decade has provided an alternative to LASIK for patients considering cornea laser refractive surgery. SMILE offers a novel approach using the femtosecond laser to create an intrastromal lenticule that can be removed through a small three to four millimeter incision. The purpose of this study is to review the recent literature on popular SMILE claims - reduced iatrogenic dry eye, better recovery of corneal sensation, and a biomechanically stronger cornea - summarize the published outcomes, and determine which claims are myths versus realities. SMILE is still in its infancy as a refractive technique in the US after recent USFDA approval for its treatment of myopia astigmatism in October 2018. Future randomized controlled studies are needed to compare its outcomes to LASIK, which has well-documented good visual outcomes, rapid postoperative recovery, and good safety profile. [ABSTRACT FROM AUTHOR]

Background: Traumatic dislocation of laser-assisted in situ keratomileusis (LASIK) corneal flaps is an uncommon postoperative complication that could occur any time after LASIK, and could be visually devastating. We evaluated the visual outcomes, corneal sensation, tear function, and dry eye questionnaire results of patients with traumatic dislocation of LASIK flaps, including one LASIK flap amputation.Methods: This is a retrospective case series. Seven patients who were diagnosed with traumatic displacement of the LASIK flap and underwent flap replacement surgery between August 2014 and January 2019 were included.Patient's visual acuity, refraction, corneal sensitivity, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH), and ocular surface disease index (OSDI) results were evaluated.Results: The patients' mean age was 35.86 ± 5.84 years, and 42.9 % (3/7) were male. The mean duration from LASIK to trauma was 8.86 ± 2.48 years.The mean preoperative and postoperative six-month corrected distance visual acuity (CDVA) were 0.55 ± 0.34 and 0.02 ± 0.03, respectively. The mean spherical equivalent and astigmatism at six months postoperatively was - 1.0 ± 0.95 D and - 0.5 ± 0.25 D, respectively. The corneal flap was clear and well-positioned at the final follow-up (mean: 28.57 ± 6.9 months). 85.71 % (6/7) of the patients showed worse corneal sensation in the injured eye. Interocular OSDI discrepancy was less in those whose last visit was more than 30 months after the trauma.Conclusions: Postoperative CDVAat six months was improved, and the refractive data also showed some improvement. The corneal nerve and tear function recovery peaked before 30 months, while the OSDI continued to show a strong trend of improvement beyond 30 months. [ABSTRACT FROM AUTHOR]

Purpose: This investigation planned to assess the impacts of Laser In Situ Keratomileusis (LASIK) with prevalent and nasal pivot areas on corneal sensation and dry eye condition. Planned randomized similar investigation was completed from February 2018 to December 2019. The subsequent term were preoperatively evaluated just as 1week and 1,3,6 months postoperatively. This examination included 600 eyes of 420 patients (180 guys and 240 females), all patients went through LASIK medical procedure for rectification of nearsightedness as well as nearsighted astigmatism utilizing MEL 90 Excimer laser for stromal removal, Moria M2, SBK microkeratomes were utilized to make a prevalent and nasal pivoted folds. At the point when patients chose to have medical procedure, they were randomized to get nasal or predominant pivot medical procedure based on the randomization succession. Focal Cochet-Hat esthesiometry, Schirmer fundamental tear discharge test, tear film separation time (TBUT) were assessed preoperatively and at multi week, 1, 3, and a half year postoperatively. After medical procedure, the corneal sensation diminished essentially in both nasal-pivot and prevalent pivot folds at multi week however got back to gauge by half year. The Schirmer essential emission test esteems were not altogether changed postoperatively in the nasal pivoted and predominant pivoted eyes. TBUT diminished inconsequential at multi week and multi month postoperatively and recouped by 3 months after medical procedure in the two gatherings. There were no huge contrasts in all the abstract and target boundaries tried between nasal-pivoted and unrivaled pivoted folds whenever point. There is no intraoperative and postoperative inconveniences in everyone’s eyes. There was a huge decrease in corneal sensation following LASIK in nasal and predominant gatherings. Sensation improved at untouched stretches and re-visitations of nearly, preoperative levels around a half year postoperatively. Related with the corneal denervation is a prompt postoperative increment in dry-eye as estimated by TBUT and schirmer test that improved utilizing oils and with ensuing visits. [ABSTRACT FROM AUTHOR]

Neurotrophic keratitis or keratopathy (NK) is a degenerative corneal disease induced by impairment of the trigeminal nerve function. This condition may lead to persistent epithelial defects, corneal ulceration, and perforation. The diagnosis of NK requires a careful investigation of any ocular and systemic condition associated with the disease and ocular surface and corneal sensitivity examinations. In the past, several medical and surgical procedures were used to treat this condition with different clinical effectiveness. Cenegermin is a recombinant human nerve growth factor (rh-NGF) that supports corneal reinnervation. Different clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis. In this review, we report the literature on clinical results regarding the treatment of NK with cenegermin since its approval by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2017 and 2018, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer IA declared a past co-authorship with the author JA to the handling editor., (Copyright © 2024 Roszkowska, Spinella, Calderone, Sindoni, Wowra, Kozak, Sajak-Hydzik and Aliò.)

Background: Corneal sensitivity can decrease by several ocular conditions , such as dry eye or refractive surgery, which favor ocular epithelial lesions and is measured using an esthesiometer. The study's primary objective was to demonstrate the efficacy and safety of the non-contact esthesiometer BRILL, which delivers air pulses to the corneal surface to assess corneal sensitivity., Methods: A single-center, prospective, controlled pilot study was carried out in adult patients with healthy eyes and or with pathology. Corneal sensitivity measurements were made in triplicate for both eyes at three consecutive visits. The esthesiometer BRILL was used in all visits , and on the last visit, the contact esthesiometer Cochet-Bonnet was also used. The results of both devices were compared by transforming them into force values., Results: 54 subjects with a mean age of 50.43 (SD 16.55, interval 18-87), 77.78% women, were included. Comparing the forces applied by both esthesiometers in the healthy eyes, in the eyes with pathology in all the groups, and in the dry eyes showed significant differences, p  = 0.03603, p  = 0.00614, and p  = 0.0001, respectively., Conclusion: The BRILL esthesiometer proved to be an effective and safe tool for non-contact assessment of corneal sensitivity with operator-independent repeatability. The measurements had a good agreement and comparable range with the Cochet-Bonet aesthesiometer measurements in healthy and dry eyes but with no interchangeable values. This portable device can help ophthalmologists and optometrists to diagnose eye pathologies that cause decreased corneal sensitivity and to assess the efficacy of therapy and disease progression., Competing Interests: Declaration of conflicting interestsJML, JL-S, and CRL have no conflicts of interest or financial ties to disclose. CGM declares that she is an employee of Brill Engines but did not receive an honorarium or another form of additional financial aid related to the development of this article.

Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n = 6 studies), dietary supplements (n = 4), anti-glycemic agents (n = 3), combination therapy (n = 3), supportive therapies (n = 2) and systemic pain pharmacotherapies (n = 2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome set. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve the capacity to synthesize data to inform evidence-based care. Protocol registration: PROSPERO ID: CRD42022348475., Competing Interests: Declaration of competing interest None for all authors., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hermann's tortoise is one of the most popular reptiles kept as pet which underlines the importance to reinforce the information needed to provide advanced and adequate veterinary care in exotic animal species. Therefore, the purpose of this study, performed in Testudo hermanni , was to evaluate corneal touch threshold (CTT) and its feasibility according to age and body weight. Fifty-one healthy tortoises were classified in 2 groups (≤2 years [young; n = 25] and 8–10 years [subadult; n = 26]). Central CTT was measured by means of a Cochet-Bonnet esthesiometer and defined as the filament length required to elicit a blink in at least 3/5 applications. CTT feasibility according to body weight was also evaluated by diving the individuals in weight groups consisting of "lighter" (<400 g [n = 31]) and "heavier" (≥400 g [n = 20]) animals. Mean CTT was 5.99 cm for the whole population (90% CI: 5.87–6.11), being 5.98 cm for young (90% CI: 5.81–6.15) and 6 cm for all subadult (90% CI: 6.00–6.00) tortoises, and 5.98 cm for lighter (90% CI: 5.84–6.13) and 6 cm for all heavier (90% CI: 6.00–6.00) tortoises. No statistical differences were detected between age and weight groups (P = 0.159 and P = 0.159, respectively). Three animals presented unilateral faint fluorescein uptake postesthesiometry (3/51; 2.9%) that resolved spontaneously within 48 hours. Cochet-Bonnet esthesiometer was a safe means of confirming high corneal sensitivity in all tortoises, which was high regardless of age. Increasing filament lengths would ultimately be required to determine the true corneal sensitivity scope of Testudo hermanni. [ABSTRACT FROM AUTHOR]

Purpose: To determine the relationship between corneal sensitivity and diabetic retinopathy among diabetics attending Lagos University Teaching Hospital, compared to their age–sex-matched non-diabetics, with a view to proposing its use as a screening tool for diabetic retinopathy. Methods: The study was a hospital-based comparative cross-sectional study among diabetics aged 25–65 years and their age–sex-matched non-diabetics at Lagos University Teaching Hospital, Lagos, Nigeria. Interviewer-based questionnaire was administered. Corneal sensitivity was assessed with Cochet-Bonnet aesthesiometer. Dilated fundoscopy examination was carried out using slit-lamp bio-microscope with 78D lens and binocular indirect ophthalmoscope. Results: A total of 120 diabetics and 120 age- and sex-matched non-diabetics were enrolled into the study. Among the diabetics, the mean corneal sensitivity was 52.6 ± 6.9 mm, which was statistically lower than among non-diabetics − 58.2 ± 3.0 mm (p-value < 0.05). Twenty-one percent of the diabetic respondents had diabetic retinopathy. The mean cornea sensitivity was statistically lower among diabetics who had developed diabetic retinopathy compared to those with no diabetic retinopathy (48.9 ± 7.3 vs. 55.3 ± 5.4, p < 0.05). The sensitivity and specificity of the aesthesiometer for proliferative diabetic retinopathy at 55 mm cut-off were 100% and 58%, respectively. Conclusion: Cornea sensitivity was significantly lower among diabetics with retinopathy compared to those without retinopathy. Also, the degree of cornea sensation loss among diabetics reduced significantly with severity of diabetic retinopathy. Larger validity studies need to be conducted to further assess the use of corneal aesthesiometer as a screening tool for diabetic retinopathy among non-ophthalmologists and other cadres of health workers. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of acute conjunctivitis on tear film characteristics and corneal sensitivity in dogs. Animals studied: Eight female spayed Beagle dogs (1.5‐2 years old, 7.5‐10 kg). Procedures: On two consecutive days, one randomly selected eye in each dog received 1 or 375 mg/mL histamine solution to induce mild or severe conjunctivitis, while the contralateral eye served as control. Diagnostic tests were performed in the following order: fluorescein instillation and repeated tear collection over 20 minutes (to determine tear volume [TV] and turnover rate [TTR] by fluorophotometry), Schirmer tear test‐1 (STT‐1), tear ferning, corneal esthesiometry, and tear film breakup time (TFBUT). Results: Results are presented as median values for severe conjunctivitis, mild conjunctivitis, and control eyes. Eyes with severe conjunctivitis had significantly higher STT‐1 (24, 19.5, 17.5 mm/min; P =.002) and significantly lower TFBUT (10.5, 13.5, 15.5 s; P =.002), but no changes were noted in corneal tactile sensation (2, 2.5, 2.5 cm) or tear ferning (grades 2, 2, 2.5). Severe conjunctivitis significantly increased TV by nearly 10‐fold (631, 97, 65 µL) initially (reflex tearing), although basal TV returned rapidly (<5 minutes) in all eyes (46, 58, 48 µL). Finally, there was a nonsignificant trend for higher reflex TTR in the conjunctivitis vs control eyes (68, 58, 43%/min). Conclusions: Experimentally induced conjunctivitis increases tear quantity and decreases tear quality in dogs, but has no impact on corneal sensitivity. Changes in tear film dynamics could affect ocular pharmacology (eg, precorneal retention time), although homeostasis of lacrimal volume and drainage is rapidly restored. [ABSTRACT FROM AUTHOR]

Background: The presence of diabetic keratopathy associated with diabetic corneal neuropathy should be taken into account in the management of corneal inflammation in patients with diabetes mellitus. Purpose: To determine the impact of adjunctive topical autologous serum eye drops on delayed healing of bacterial corneal ulcers in patients with type 1 diabetes mellitus (DM1). Material and Methods: We retrospectively reviewed the results of observing 19 DM1 patients (19 eyes) with bacterial corneal ulcers who exhibited delayed healing of corneal ulceration and whose corneal smears and scrapings taken one week after initiation of treatment were bacteriologically negative. Patients had a routine eye examination (visual acuity, tonometry, and slit-lamp biomicroscopy of anterior and posterior eye segments), bacteriological studies, fluorescein dye test, anterior eye OCT and noncontact corneal esthesiometry. Patients of the control group (9 individuals) continued receiving only background therapy (topical antiseptics, antioxidants, repairing agents, artificial tears, and mydriatics and systemic anti-inflammatory agents), whereas patients of the main group began receiving autologous serum eye drops in addition to background therapy of topical antiseptics, mydriatics and systemic anti-inflammatory agents. Clinical picture data for day 1 (visit 1, before administering the treatment) and days 7 (when corneal samples and scrapings were re-taken), 14 (when bacteriology results became available and main group patients were additionally administered autologous serum), 17, 21 and 24 were analyzed. Results: In DM1 patients with delayed healing of bacterial corneal ulcers, the use of adjunctive autologous serum eye drops after eradication of the offending microorganisms resulted in reductions in precorneal injection and size and depth of the ulcer defect and complete resolution of corneal infiltration and edema of the corneal tissue surrounding the ulcer as early as day 3, and recovery of all patients and a 32.6% improvement in corneal sensitivity on day 10. Conclusion: Using adjunctive topical autologous serum eye drops after eradication of the offending microorganisms was found to be efficacious in the comprehensive treatment of delayed healing of bacterial corneal ulcers in patients with DM1. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy.Methods: This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups.Results: 29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p < 0.0001; controls, < 0.0001-0.03); improvement at month 18 vs baseline was higher in Cit-B12 than placebo (33% vs 15%, p = 0.04). A progressive amelioration of corneal sensitivity (baseline, 28 ± 18 mm; month 18, 52 ± 10 mm, p < 0.0001), conjunctival staining (P = 0.04) and OSDI questionnaire (P = 0.05) were shown on Cit-B12 group alone. Both treatments were well tolerated and adherence during the study was high.Conclusions: Cit-B12 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroregenerative effect.Trial Registration: Trial registration NCT03906513 , retrospectively registered on 08 April 2019. [ABSTRACT FROM AUTHOR]

Ocular examinations were completed on a group of 10 Atlantic puffins (Fratercula arctica), 5 males and 5 females that ranged in age from 8 months to older than 30 years. The exams consisted of intraocular pressure/rebound tonometry, tear production/phenol red thread test, central corneal thickness/ultrasound pachymetry, and corneal sensitivity/esthesiometry. On ocular examination, there were no corneal abnormalities observed. Bilateral cataracts were diagnosed in 8 puffins, 6 of which were considered incipient, focal subcapsular opacities. One bird had hypermature cataracts and was removed from the study and excluded from data analysis; the other birds had no evidence of ophthalmic pathology that would interfere with diagnostic results (n = 9). All results for 9 birds were included in the study, with the exception of 1 puffin's tear production, which was too low for accurate assessment and was excluded from data analysis. There were no significant differences between right and left eye measurements for intraocular pressure, corneal thickness, and corneal sensitivity. The median intraocular pressure for both eyes (OU) was 13 mm Hg with an interquartile range [IQR] of 12–15 mm Hg. The median corneal thickness OU was 241 µm, IQR 233–248 µm. The median corneal sensitivity OU was 1.13 cm, IQR 0.81–1.50 cm. There was a significant difference between right and left eye measurements for tear production (right eye median, 7.5 mm/15 s, IQR 6.5–9.3 mm/15 s; and left eye median, 5.0 mm/15 s, IQR 4.0–7.3 mm/15 s) (P=.03), with the right eye producing more tears than the left. However, 1 puffin was determined to be an outlier, and when removed, there was no longer a significant difference (OU median, 7.0 mm/15 s, IQR 4.6–8.0 mm/15 s) (P =.38). There was no significant difference between sex and intraocular pressure, tear production, and corneal sensitivity. However, there was a significant difference between sex and corneal thickness (P =.02), with males (left eye median, 249 µm, IQR 241–249 µm) having thicker corneas than females (left eye median, 236 µm, 234–238 µm). Although sample size precluded statistical testing, there appeared to be an association between opacities and increasing age. There were no associations between age and intraocular pressure, tear production, or corneal thickness. There was a moderate correlation between age and corneal sensitivity, with older birds showing decreased corneal sensitivity (r = –0.57). Although the sample size of 9 birds was small, these findings provide preliminary ranges for ocular parameters of Atlantic puffins. [ABSTRACT FROM AUTHOR]