Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin).

PURPOSE: To evaluate corneal healing in patients with moderate and severe neurotrophic keratitis (NK) treated with topical rh-NFG (Cenegermin). METHODS: Twenty-one patients (12F and 9M) aged from 21 to 93 years (62.5 ± 19.4) with moderate and severe NK were enrolled in the study. The patients were divided into 2 groups accordingly to the severity of the disease. The underlying causes of NK were determined. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The drops of Cenegermin 0.002% were administrated 6 times daily for 8 weeks. All participants were evaluated at baseline, after 4 and 8 weeks of the treatment. The area of corneal defect with maximum diameter less than 0.5 mm was considered as healed. The main outcome measures were corneal healing, corneal sensitivity recovery and corneal thickness in the ulcer group. RESULTS: The herpetic keratitis was the most common cause of NK. Thirteen eyes were affected by severe grade of NK with corneal ulcer and 8 eyes presented a moderate grade. After 8 weeks a complete healing of the corneal defects was registered both in moderate and severe NK. Significant increase of the corneal sensitivity and thickness were registered. CONCLUSIONS: The rh-NGF (Cenegermin) resulted effective in the treatment of the severe and moderate NK with significant recovery of the corneal sensitivity and healing of the corneal defects in both groups.

Effects of the Topical Use of the Natural Antioxidant Alpha-Lipoic Acid on the Ocular Surface of Diabetic Patients with Dry Eye Symptoms.

PURPOSE: The purpose of this study is to investigate the effects of the treatment with eye-drops based on a combination of antioxidant and mucomimetic molecules, namely 0.1% alpha-lipoic acid (ALA) and 0.3% hydroxy-propyl-methylcellulose (HPMC) on the ocular surface of diabetic patients with dry eye symptoms. METHODS: Seventy patients, 42 M and 28 F, aged from 50 to79 years (mean 62.1 ± 10.5), affected by type II diabetes mellitus, were enrolled and divided in two groups treated for 2 months as follows: Group 1 (35 patients), received topical ALA/HPMC three times a day, Group 2 (35 patients) received topical HPMC (0.3%) alone, three times a day. The main outcome measures were: Ocular Surface Disease Index (OSDI), tear film break-up time (TBUT), corneal fluorescein staining, Schirmer I test, corneal sensitivity. An examination of tear film morphology with confocal microscopy was carried out in a subset of patients of each group at baseline and after two months. Statistical analysis was performed with t-test for the parametric data and Mann-Whitney U-test or chi-squared test for the nonparametric data. RESULTS: Both treatments resulted in significant improvements of BUT, OSDI and tear film morphology, although the improvements observed in group 1 showed a higher trend than what observed for group 2. Moreover, only in group 1 a significant improvement was visible for corneal staining, and no significant improvements were observed in any group for Schirmer I and sensitivity. CONCLUSIONS: These results confirmed the efficacy of HPMC in the treatment of diabetic dry eye and indicated that the addition of a strong self-regenerating antioxidant like ALA may give a distinctive advantage for the healing of corneal defects (as evidenced by corneal staining), beside improving HPMC efficacy on three other parameters (BUT, OSDI score, tear morphology). Therefore, the addition of a strong antioxidant like ALA can be helpful in preventing or treating ocular surface defects in diabetic patients, in which the oxidative damage is predominant.

The Role of Hi-Tech Devices in Assessment of Corneal Healing in Patients with Neurotrophic Keratopathy.

To prove the role of high-tech investigation in monitoring corneal morphological changes in patients with neurotrophic keratopathy (NK) using Keratograph 5M (K5M) and anterior segment OCT (AS-OCT), corneal healing was monitored with Keratograph 5M (Oculus, Wetzlar, Germany) and AS-OCT (DRI, Triton, Topcon, Tokyo, Japan) in 13 patients (8F and 5M), aged from 24 to 93 years (67.8 ± 19) with severe NK, who were treated with Cenegermin 0.002% (20 µg/mL) (Oxervate®, Dompè, Farmaceutici Spa, Milan, Italy). The surface defects were evaluated on Keratograph 5M with ImageJ software and the corneal thickness variations were measured using DRI-Triton OCT software. Instrumental procedures were performed at baseline, and after 4 and 8 weeks of the treatment, respectively. The main outcome measures were reduction of the ulcers' area and corneal thickness recovery. The mean area of the corneal ulcers was reduced between baseline and 4 weeks examination in all patients, and at 8 weeks all ulcers were completely healed. An increase of the corneal thickness was evidenced between the baseline visit and after the 4- and 8-week follow-up, respectively. Additionally, only in collaborating subjects the In Vivo Confocal Microscopy (IVCM) was performed with HRT Rostock Cornea Module (Heidelberg Eng GmbH) to study the corneal nerves fibres. High-tech diagnostics with K5M, AS-OCT and IVCM proved useful in the assessment of corneal morphology and the healing process in patients with NK and could be extended to assess other corneal pathologies.

Corneal nerves in diabetes-The role of the in vivo corneal confocal microscopy of the subbasal nerve plexus in the assessment of peripheral small fiber neuropathy.

The cornea's intense innervation is responsible for corneal trophism and ocular surface hemostasis maintenance. Corneal diabetic neuropathy affects subbasal nerve plexus, with progressive alteration of nerves' morphology and density. The quantitative analysis of nerve fibers can be performed with in vivo corneal confocal microscopy considering the main parameters such as corneal nerve fibers length, corneal nerve fibers density, corneal nerve branching density, tortuosity coefficient, and beadings frequency. As the nerve examination permits the detection of early changes occurring in diabetes, the invivo corneal confocal microscopy becomes, over time, an important tool for diabetic polyneuropathy assessment and follow-up. In this review, we summarize the actual evidence about corneal nerve changes in diabetes and the relationship between the grade of alterations and the duration and severity of the disease. We aim at understanding how diabetes impacts corneal nerves and how it correlates with sensorimotor peripheral polyneuropathy and retinal complications. We also attempt to analyze the safety of the most common surgical procedures such as cataract and refractive surgery in diabetic patients and to highlight the specific risk factors. We believe that information about the corneal nerve fibers' condition obtained from the in vivo subbasal nerve plexus investigation may be crucial in monitoring peripheral small fiber polyneuropathy and that it will help with decision-making in ophthalmic surgery in diabetic patients.

Combined Phialemonium curvatum and Acanthamoeba Keratitis: The Importance of Early Diagnosis and Specific Therapy.

PURPOSE: To report the clinical and confocal findings of a unique case of combined Phialemonium curvatum and Acanthamoeba keratitis and to highlight the role of the prompt diagnosis and specific medical treatment in preserving visual function. METHODS: A case report and literature review. RESULTS: A 54-year-old woman presented with a 3-day history of visual impairment, photophobia, and ocular pain in her right eye. Her best corrected visual acuity was 0.4 Logarithm of the Minimum Angle of Resolution scale, and the slit-lamp examination showed whitish corneal stromal infiltrate with satellite lesions. In vivo confocal microscopy evidenced Acanthamoeba cysts and fungal hyphae that resulted P. curvatum in the culture examination. The intensive medical treatment was started with topical 0.02% polyhexamethylene biguanide, voriconazole 1%, and moxifloxacin hydrochloride 0.5%. Progressive improvement of clinical and confocal pictures was registered with a complete recovery of visual function after 1 month. CONCLUSIONS: This is the first case report of combined P. curvatum and Acanthamoeba keratitis. The fast diagnosis with in vivo confocal microscopy allowed early and intensive specific treatment with recovery of corneal infection.

Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye.

PURPOSE: Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10). METHODS: Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed. RESULTS: At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination. CONCLUSIONS: The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.

Comparative Confocal and Histopathological Study of Corneal Changes in Multiple Myeloma.

PURPOSE: Corneal opacities rarely occur in multiple myeloma (MM). Our study correlates the findings of in vivo confocal microscopy (IVCM), a useful diagnostic tool, with histopathological features of corneal opacities appearing in a patient with MM. METHODS: Case report. RESULTS: A 53-year-old man developed corneal opacities in both eyes, more pronounced in the left eye. After IVCM examination, he underwent penetrating keratoplasty in the left eye, and the button was processed for light and electron microscopy and immunohistochemistry. The diagnosis of MM was made, as confirmed by the elevation of IgGk light chains. IVCM demonstrated hyperreflective areas at the epithelial level, hyperreflective keratocytes of dendritic and lamellar morphology in whole stroma, and hyperreflective endothelial cells. Histopathological examination disclosed many vacuoles in the epithelial cell cytoplasm and a homogenous granular material in the Bowman layer. In stroma, keratocytes of different shape and size, with vesicles laden with an abnormal material, were evident. In Descemet membrane, the posterior nonbanded zone had a honeycomb appearance because of the presence of many roundish spaces among wide-spaced collagen fibers. Endothelial cells demonstrated vesicles filled with a material of uneven electron density. Immunohistochemical analysis showed strong positivity for IgGk light chains in keratocytes and among stromal lamellae. CONCLUSIONS: This is the first study describing a correspondence between IVCM features and histopathological alterations observed in corneal opacities in MM. The results of this study improve the current understanding of the pictures obtained by IVCM studies.