New disposable esthesiometer (KeraSenseⓇ) to improve diagnosis and management of neurotrophic keratitis.

PURPOSE: To validate the use, repeatability, and reproducibility of a new, cost-effective, disposable, sterile device (KeraSenseⓇ, Dompè farmaceutici SpA, Milan Italy) compared to Cochet-Bonnet (CB) esthesiometer. Secondly, to identify a simple, safe, rapid, and low-cost test to diagnose neurotrophic keratitis (NK). METHODS: 16 patients with diagnosis of NK stage I, 25 patients with diabetes mellitus (DM), and 26 healthy subjects were included in the study. Corneal sensitivity (CS) was assessed by CB and KeraSenseⓇ. Repeatability, accuracy, and reproducibility of the novel disposable aesthesiometer were assessed. Specificity, sensitivity, and cut-off value for NK diagnosis were calculated by ROC curve analysis. RESULTS: All NK patients showed a CS ≤ 40 mm, while none of the healthy patients showed a CS value < 50 mm. Significant agreement was found between CB measurements and the single use esthesiometer evaluations of CS (p < 0.001). Repeatability evaluations of the single use esthesiometer showed 100% agreement between different measurements (p < 0.001). Reproducibility evaluations showed 99.6% concordance between different operators (p < 0.001). A 55 mm value of the single use esthesiometer was adequate to exclude an NK diagnosis, while all NK patients showed a value ≤ 35 mm. CONCLUSIONS: Corneal hypo/anaesthesia is considered the hallmark of NK. The use of the novel single-use esthesiometer will allow for a diagnostic improvement in NK, sparing time and guaranteeing patients' safety. Diabetic patients despite normal corneal findings may show impairment of CS, suggesting a preclinical stage of NK, requiring a close follow-up.

OCT biomarkers as predictors of visual improvement in diabetic macular edema eyes receiving dexamethasone implants.

BACKGROUND: Several optical coherence tomography (OCT) biomarkers have been proposed as predictors for functional and anatomical outcomes in Diabetic Macular Edema (DME). This study aims to examine the impact of these OCT features on the visual acuity improvement of patients with DME after long-acting Dexamethasone intravitreal implants (DEX-I) injection. Furthermore, the safety and impact of DEX-I on clinical parameters, including intraocular pressure (IOP) were assessed. METHODS: In this retrospective observational study, we reviewed the medical records of naïve and non-naïve eyes with DME who received at least one DEX-I. The primary endpoint was visual acuity improvement of ≥ 5 ETDRS letters at 1 month and 4 months after treatment. Secondary outcomes were the changes in OCT biomarkers and the impact of DEX-I on IOP at 1 and 4 months of follow-up. Linear panel regression analysis was used to test for differences in central subfield thickness (CST) over time and it was stratified according to biomarkers at baseline. Finally, a logistic regression analysis was used to identify factors predicting visual improvement at 1 and 4 months. RESULTS: We included 33 eyes of which 63.6% were at an advanced stage of DME. Overall, CST, cube average thickness (CAT), cube volume (CV), and intraretinal cystoid spaces > 200 µm (ICS) decreased following DEX-I injection (p < 0.001). Additionally, a thicker CST at baseline was observed in eyes with better visual improvement at one month (p = 0.048). After logistic regression analysis, CST was retained as the only predictor for visual improvement at one month (p = 0.044). Furthermore, panel regression analysis identified a relation between subfoveal neuroretinal detachment (SND) at baseline and CST increase at four months. Lastly, only 15.2% of the eyes necessitated topical medication for IOP reduction, with no differences observed when stratifying between naïve and non-naïve eyes. CONCLUSION: Our analyses suggest that a ticker baseline CST may serve as a positive predictor of early visual improvement and SND presence at baseline may be a negative prognostic factor for CST increase 4 months after DEX-I injection. Other well-known biomarkers, such as disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HF), did not demonstrate prognostic value on visual outcomes, at least within the first four months following the injection.

Does choroidal thickness predict persistent subretinal fluid after rhegmatogenous retinal detachment repair? A retrospective study with fellow eye comparison.

PURPOSE: To evaluate whether choroidal thickness (CT) is associated with persistent subretinal fluid (pSRF) after simple primary rhegmatogenous retinal detachment (RRD) repair. METHODS: This single-centre, retrospective, observational study included patients who underwent RRD repair with at least 12-month follow-up. Preoperative and postoperative parameters were evaluated for association with pSRF. CT measurements were obtained at the central 1 mm area on enhanced depth imaging (EDI) OCT scans, using a semiautomatic method. Multiple logistic regression analyses were assessed to determine predictive factors for pSRF. RESULTS: Overall, 100 eyes of 100 patients, mean age of 59.9 ± 12.6 years were included. pSRF was found in 21.0% of eyes and resolved over time in 85.7% of eyes at 12 months. In the pSRF group both RRD and fellow eyes showed lower mean choroidal and RPE thickness values as compared to those without pSRF (p < 0.05). A significant correlation was found between pSRF occurrence and choroidal thinning (p = 0.02). After multiple regression analyses, macula-off RRD (p = 0.005) and scleral buckling (SB) technique (p = 0.001) were retained as final predictors for pSRF. In macula-off SB eyes, detachment duration was the only factor associated with pSRF (p = 0.046). There were no significant differences in best-corrected visual acuity outcomes between the pSRF and the no-pSRF eyes. CONCLUSIONS: Patients with pSRF showed lower choroidal and RPE thickness as compared to those without pSRF. CT did not turn out to be a final predictor for pSRF, as this was mainly associated with macular involvement, surgical technique and detachment duration.

Autophagy-lysosome pathway alteration in ocular surface manifestations in Fabry disease patients.

BACKGROUND: Fabry disease (FD) is a rare X-linked, lysosomal storage disorder caused by mutations in the alpha-galactosidase gene and characterized by neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and ocular manifestations. The aim of this study is to characterize morphological, functional and autophagy-lysosome pathway alterations of the ocular surface in FD patients. METHODS: Eleven subjects with a diagnosis of FD and fifteen healthy control subjects were examined. All patients underwent ocular surface slit lamp examination, corneal aesthesiometry and in vivo confocal laser-scanning microscopy (CCM). Conjunctival impression cytology was performed in six FD patients and six controls, to assess for expression of two markers of the autophagy-lysosome pathway: the microtubule-associated protein light chain 3 (LC3) and lysosome-associated membrane protein 2 (LAMP2). RESULTS: Cornea verticillata and increased conjunctival vessel tortuosity were detected respectively in 67% and 33% of patients with FD. Compared with healthy subjects, patients affected by FD showed a significant reduction in corneal nerve fiber length, density and nerve branching on CCM and a significantly increased expression of LC3 on conjunctival impression cytology (p < 0.001). No changes were observed in the conjunctival expression of LAMP2 between the two groups. CONCLUSIONS: This study shows that FD is associated with ocular surface alterations including corneal and conjunctival morphology, innervation and vascularization changes. Our data demonstrate an increased expression of LC3 protein in patients with FD, suggesting that alteration of the autophagy-lysosome pathway may play a role in the occurrence of ocular manifestations.

Management Strategies of Juvenile Idiopathic Arthritis-Associated Chronic Anterior Uveitis: Current Perspectives.

Juvenile idiopathic arthritis (JIA) is the most common extraocular disease associated with pediatric uveitis. Despite the growing knowledge about the pathogenetic and clinical characteristics of the disease, it still remains a challenge for both the pediatric rheumatologist and ophthalmologist. Since uveitis is asymptomatic in most cases, it is generally detected by parents in a late phase of the disease when complications have occurred with consequent severe vision loss. Improvement in attentive screening and early treatment initiation to suppress inflammation has considerably reduced the sight-threatening outcomes of JIA-associated chronic anterior uveitis (JIA-CAU). Initial treatment with topical steroids is effective in most cases. However, more severe cases require the use of periocular or systemic corticosteroids, possibly leading to long-term complications. These include growth retardation, cataract and glaucoma. Systemic immunosuppressive agents are then employed in patients resistant to first-line therapy or to reduce steroid-associated complications. In this review, we will discuss the immunosuppressant agents currently employed for the treatment of the disease, including anti-tumor necrosis factor (TNF)α biologics approved or not by the regulatory agencies. We will also highlight how new therapeutic options like biologic targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) co-stimulatory molecule, interleukin-6 receptor (IL-6R) or B lymphocytes might represent exciting new options for patients resistant to conventional therapy. Finally, the potential use of janus kinase (JAK) inhibitors recently approved for the treatment of several inflammatory rheumatic diseases in adults will be also discussed.

Obstructive sleep apnoea patients vs laryngopharyngeal reflux disease: Non-invasive evaluation with NBI and pepsin detection in tears.

Obstructive sleep apnoea (OSA) and laryngopharyngeal reflux disease (LPR) are two common diseases that lower patients' quality of life. OSA is defined by cyclic events of airflow obstruction that occur during sleep, while LPR is characterized by upper airway inflammatory signs and symptoms due to the return of gastroduodenal gaseous and liquid elements. pH-metry is the gold standard in LPR diagnosis, but considering its invasiveness among other negative traits, questionnaires that catalog symptoms and signs of the disease such as Reflux Symptoms Index (RSI) and Reflux Finding Score (RFS) are preferred. Moreover, LPR can be evaluated by testing the presence of pepsin in tears, and Narrow Band Imaging (NBI) has been introduced for the early diagnosis of larynx oncological disease. This paper aims to test whether LPR is more frequent in OSA patients than in control ones, performing a non-invasive protocol composed of RSI, RFS test (with light vs. NBI techniques), followed by pepsin detection in tears. 68 LPR patients were enrolled in the study (45 with OSA and 23 without OSA). A strong linear relationship between Apnea-Hypopnea Index (AHI) and Oxygen Desaturation Index (ODI) was found, and patients who presented pepsin in tears had higher values of AHI and ODI in comparison to patients without it. Pathological RFS and NBI showed higher values of AHI and ODI in comparison to the control group. Furthermore, pathological RSI showed higher values of AHI and ODI in comparison to the control group. In conclusion, this diagnostic combined non-invasive protocol may be a good method to perform an early diagnosis of LPR.

Main Complications of Photorefractive Keratectomy and their Management.

Photorefractive keratectomy (PRK) was the first surface ablation procedure introduced for the treatment of refractive errors and has been proven to be effective and safe. In some cases, however, the patient may not be totally satisfied with the final result and retreatment may be necessary. We performed a literature review to describe the main conditions that may arise following PRK that may require retreatment and new promising techniques to allow customized and effective treatments for patients. There is currently no gold standard for retreatment of residual refractive error after PRK. The surgeon must take into account the patient's history and type of problem when choosing the most appropriate technique. LASIK and PRK are the main options. Haze can be treated with good results with phototherapeutic keratectomy and mytomicin C. High order aberrations and decentration may be addressed with topographically-guided excimer photoablation or with wavefront-guided PRK.

Eye drop emulsion containing 0.1% cyclosporin (1 mg/mL) for the treatment of severe vernal keratoconjunctivitis: an evidence-based review and place in therapy.

Vernal keratoconjunctivitis (VKC) is a rare, recurrent and multifactorial ocular disease, which typically flares up during spring and affects especially male children and adolescents. This condition does not usually respond to common treatments with antihistamines or mast cells stabilizers, whereas corticosteroids have effective results. Corticosteroids need to be carefully administered, to avoid adverse effects, mainly the secondary development of glaucoma, cataracts, or infections. Immunosuppressive agents, such as cyclosporin (CyA) or tacrolimus are, therefore, frequently employed in VKC patients. Only the 0.1% CyA (1 mg/mL) concentration has an approved and specific clinical indication for the treatment of VKC and this drug was given the denomination of orphan drug by the European Commission (EU/3/06/360) in 2006. So far, few studies have been conducted to evaluate the efficacy and the side effects of topical 0.1% CyA. Different topical CyA concentrations, ranging from 0.05% to 2%, and various types of formulation are available at the moment. In the future, 0.1% CyA will presumably take an important part in the management of VKC. The present review focuses on eye drops containing 0.1% CyA; however, more studies will be needed to define its long-term efficacy in the natural course of this severe ocular disease.