A pilot study on Langerhans cells in keratoconus patients by in vivo confocal microscopy before and after corneal cross-linking and correlation with eye rubbing.

PURPOSE: The aim of this study was to investigate the corneal microstructure and Langerhans cells using in vivo confocal microscopy in keratoconus patients before and after cross-linking, and to correlate the morphologic findings with clinical and patient-reported outcomes, including eye rubbing (ER) behavior. METHODS: Patients with progressive keratoconus undergoing iontophoresis-assisted epithelium-on cross-linking (I-CXL) were consecutively enrolled. In vivo confocal microscopy was performed before and 6 months after treatment. Patients were asked to quantify their ER behavior on a Visual Analogue Scale (VAS) and completed the Keratoconus Outcomes Research Questionnaire and the Ocular Surface Disease Index questionnaires at the same time points. Visual acuity, tear osmolarity, topography, aberrometry, and pachymetry of both eyes were assessed. RESULTS: Thirteen patients were included in this pilot study. Preoperatively, the mean Langerhans cells density was 35,615 cells per mm2, and the median morphology was 3. The mean ER VAS before treatment was 7,077 out of 10. The ER VAS showed significant positive correlations with both Langerhans cells density and morphology of the study eye. After treatment, a statistically significant reduction in ER VAS and in Langerhans cells variables was observed. The mean sub-basal plexus nerve density was comparable to pre-operative values 6 months after I-CXL. CONCLUSIONS: Based on this preliminary evidence, the presence of high density of mature Langerhans cells in the central cornea of keratoconus patients and its correlation with eye rubbing support the role of inflammation in keratoconus. The reduction in these markers after treatment may suggest a potential of CXL in moderating immune-related inflammation and eye rubbing in the medium term.

UHFUS: A Valuable Tool in Evaluating Exocrine Gland Abnormalities in Sjögren's Disease.

Sjögren's Disease (SjD) is a chronic autoimmune disorder that affects the salivary and lacrimal glands, leading to xerostomia and xerophthalmia. Ultrasonography of Major Salivary Glands (SGUS) is a well-established tool for the identification of the salivary glands' abnormalities in SjD. Recently, a growing interest has arisen in the assessment of the other exocrine glands with ultrasonography: lacrimal glands (LGUS) and labial salivary glands (LSGUS). The objective of this study is to explore the practical applications of ultra-high frequency ultrasound (UHFUS) in the assessment of lacrimal glands and labial salivary glands. Indeed, UHFUS, with its improved spatial resolution compared to conventional ultrasonography, allows for the evaluation of microscopic structures and has been successfully applied in various medical fields. In lacrimal glands, conventional high-frequency ultrasound (HFUS) can detect characteristic inflammatory changes, atrophic alterations, blood flow patterns, and neoplastic lesions associated with SjD. However, sometimes it is challenging to identify lacrimal glands characteristics, thus making UHFUS a promising tool. Regarding labial salivary glands, limited research is available with conventional HFUS, but UHFUS proves to be a good tool to evaluate glandular inhomogeneity and to guide labial salivary glands biopsy. The comprehensive understanding of organ involvement facilitated by UHFUS may significantly improve the management of SjD patients.

Short-term results of a pulsed therapy with hydrocortisone eye drops to treat moderate to severe dry eye in primary Sjögren syndrome patients.

BACKGROUND: We investigated the safety and efficacy of short-term treatment with topical low-dose hydrocortisone sodium phosphate 0.335% (PFH) in patients with moderate to severe primary Sjögren syndrome (SS)-related dry eye disease (DED). METHODS: A retrospective single-centre interventional study. All patients received PFH for 6 days with a pulsed posology: three times daily for 2 days, twice daily for 2 days, and once daily for 2 days. This scheme was repeated for 3 consecutive months and then alternated for 3 months. Data were collected at baseline, 3 months, and 6 months of follow-up. RESULTS: A total of 40 SS patients were enrolled. Conjunctival hyperaemia and corneal-conjunctival stain significantly improved (p < 0.001). Ocular Surface Disease Index score reduced significantly between baseline and 3 months and between baseline and 6 months (p < 0.001). The tear film osmolarity lowered significantly in each eye from baseline to 3 months and from baseline to 6 months (p = 0.002 and p = 0.037, respectively). Comparing results at 3 and 6 months, the Ocular Surface Disease Index score (p = 1.000), the frequency of lacrimal substitutes installation (p = 0.632), and tear film osmolarity (right eye p = 0.518, left eye p = 1.000) did not change significantly. Intraocular pressure did not change during the study period. CONCLUSION: PFH eye drops with a pulsed posology improve signs and symptoms, not affecting the intraocular pressure in SS-related DED. Therefore, this pulsed treatment is safe and efficacious.

Impact of corneal collagen cross-linking on vision-related quality of life measured with the keratoconus outcomes research questionnaire (KORQ) in patients with keratoconus.

PURPOSE: To assess the impact of corneal collagen cross-linking on self-reported vision-related quality of life (VR-QoL) in keratoconus patients by means of the Keratoconus Outcomes Research Questionnaire (KORQ), a new disease-specific patient reported outcomes measures (PROMs) tool. METHODS: Patients with progressive keratoconus undergoing corneal collagen cross-linking were consecutively enrolled. Patients completed the KORQ before and after the treatment, at 1, 3 and 6 months. Data were collected regarding the visual acuity and the topographic, aberrometric and pachymetric parameters of both eyes. Patients were also asked to quantify their eye rubbing behavior on a Visual Analogue Scale (VAS) from 0 to 10, before and 6 months after treatment. The KORQ scores were associated with the visual acuity, topographic, aberrometric and pachymetric data by means of the Spearman correlation coefficient. RESULTS: The Activity Limitation (AL) subscale score was higher after surgery. Preoperatively, negative correlations were observed between the KORQ AL score and Best Corrected Visual Acuity (logMAR), maximum keratometry, flattest keratometry, steepest keratometry, symmetry index front and higher order aberrations (HOA) of the treatment eye. Postoperatively, we observed a shift toward the fellow eye, with stronger correlation of the KORQ scores with the fellow eye parameters. The Symptoms subscale score correlated with the aberrometric parameters of both eyes at various time points. Statistically significant correlations were observed between the change in KORQ scores and the change in aberrometric parameters. A statistically significant reduction in the eye rubbing behavior was detected (p < 0,0001). CONCLUSIONS: These results suggest that the corneal cross-linking treatment is effective both in improving the subjective perception of the disease by the patient and in stabilizing the objective indicators of disease progression. Keratometric, aberrometric and visual acuity values showed a significant impact on self-reported VR-QoL. Corneal cross-linking, by halting the worsening of these parameters, may bear a beneficial effect on VR-QoL.

The Management of Dry Eye Disease: Proceedings of Italian Dry Eye Consensus Group Using the Delphi Method.

Dry eye disease (DED) is a highly prevalent, chronic and progressive condition that affects 5-33% of the world's adult population [...].

Ocular toxoplasmosis, an overview focusing on clinical aspects.

Toxoplasma gondii is a widespread protozoan parasite infecting approximately one third of the world population. After proliferation of tachyzoites during the acute stage, the parasite forms tissue cysts in various anatomical sites and establishes chronic infection. Nowadays the nature of the interplay between the protozoan and its human host remains elusive. This is clearly evident in ocular toxoplasmosis, in which the parasite establishes an ambivalent relationship with the eye, manipulating the immune response and inducing variable initial lesions and further relapses. This review will focus on epidemiology and environmental, parasite and host related risk factors, clinical manifestations and laboratory findings, treatment and prophylaxis approaches in ocular toxoplasmosis. An image collection of patients referred to the Unit of Ophthalmology of Pisa's Hospital will be presented, too.

Fabry disease due to G171S GLA mutation: An atypical small nerve fiber sparing variant?

INTRODUCTION: To describe the ocular manifestations and in vivo confocal microscopic findings in a patient carrying the recently described hemizygous G171S GLA gene mutation. CASE DESCRIPTION: A 63-year-old Albanian male patient was evaluated for cataract surgery. Anamnesis showed pacemaker implantation in left ventricular hypertrophy, chronic kidney disease, family history for kidney transplantation, and late onset of sporadic acroparesthesias. Bilateral cornea verticillata, and increased tortuosity in conjunctival and retinal vessels were present. In vivo confocal microscopy revealed clusters of hyper-reflective corneal epithelial cells centripetally extending from the limbus. Interestingly, the nerve fiber number, density, and length in the corneal sub-basal nerve plexus were preserved. Alpha-galactosidase A activity was almost absent and hemizygous c.511G>A mutation (G171S - p.Gly171Ser) of the GLA gene was identified. The patient was referred for initiation of enzyme replacement therapy, and genetic counseling was recommended for at-risk family members. CONCLUSION: This is the third reported case of Fabry disease due to GLA G171S mutation. All patients are of Albanian descent. Cornea verticillata and vascular anomalies remain common ocular manifestations, as well as cardiac and renal involvement. Confirming its pathogenicity, this mutation results in a "classic" Fabry disease phenotype, but it seems to be associated with a relative small nerve fiber sparing that may delay a correct diagnosis. The diagnosis of Fabry disease still remains challenging due to its clinical heterogeneity, but a thorough ophthalmological examination can promote early detection and, consequently, early initiation of enzyme replacement therapy.

In vivo confocal scanning laser microscopy in patients with primary Sjögren's syndrome: A monocentric experience.

AIMS: (i) To analyze the in vivo corneal structure and sub-basal plexus nerves in patients with primary Sjögren's syndrome (pSS) and no-SS dry eye by confocal scanning laser microscopy (CSLM) and (ii) to correlate CSLM findings with tear function tests and with patients' subjective dryness. METHODS: Seventeen patients with pSS, 16 no-SS dry eye, and 20 healthy volunteers were included. CSLM parameters taken into consideration included: basal epithelial integrity, corneal thickness, epithelial cellular density, keratocyte activation, and sub-basal plexus morphology. Statistical analysis was carried out using SPSS-13 (Chicago IL, USA). RESULTS: CSLM pachymetric data and the superficial epithelium cell density were significantly lower in pSS versus no-SS dry eye (p < 0.0001); keratocyte activation and sub-basal nerve abnormalities were also more frequent in pSS patients (p < 0.0001). CSLM findings well correlated with both the ocular test results and the patients' perception of ocular dryness at the baseline and over the follow-up. CONCLUSION: CSLM might be a useful novel tool in the assessment of the involvement of the lachrymal functional unit in pSS.

Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells.

AIM: Limbal cultures restore the corneal epithelium in patients with ocular burns. We investigated the biological parameters instrumental for their clinical success. METHODS: We report a long-term multicenter prospective study on 152 patients carrying corneal destruction due to severe ocular burns, treated with autologous limbal cells cultured on fibrin and clinical-grade 3T3-J2 feeder cells. Clinical results were statistically evaluated both by parametric and nonparametric methods. RESULTS: Clinical outcomes were scored as full success, partial success and failure in 66.05, 19.14 and 14.81% of eyes, respectively. The total number of clonogenic cells, colony size, growth rate and presence of conjunctival cells could not predict clinical results. Instead, the clinical data provided conclusive evidence that graft quality and likelihood of a successful outcome rely on an accurate evaluation of the number of stem cells detected before transplantation as holoclones expressing high levels of the p63 transcription factor. No adverse effects related to the feeder layer have been observed and the regenerated epithelium was completely devoid of any 3T3-J2 contamination. CONCLUSION: Cultures of limbal stem cells can be safely used to successfully treat massive destruction of the human cornea. We emphasize the importance of a discipline for defining the suitability and the quality of cultured epithelial grafts, which are relevant to the future clinical use of any cultured cell type.