Autoantibodies Against Trisulfated Heparin Disaccharide and Fibroblast Growth Factor Receptor-3 May Play a Role in the Pathogenesis of Neuropathic Corneal Pain.

PURPOSE: The aim of this study was to describe cases of patients with presumable dysimmune small-fiber neuropathy (SFN)-related neuropathic corneal pain (NCP), presenting with autoantibodies against trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor-3 (FGFR-3). METHODS: This study was a case series of 3 patients with NCP with positive anti-TS-HDS and/or anti-FGFR-3 autoantibodies and systemic SFN as confirmed by positive skin biopsy results. RESULTS: All 3 patients were women with a mean age of 34.3± 6.1 years. They suffered from moderate to severe persistent chronic ocular discomfort (10/10, 10/10, and 9/10 on a visual analogue scale, respectively). Although 1 patient suffered from ocular pain and photophobia alone, the other 2 patients experienced additional non-ocular pain. One of the patients had pain on her face and head, and 1 patient reported neck and lower back pain. Two patients had high anti-TS-HDS IgM titers, whereas 1 patient had both high anti-TS-HDS IgM and anti-FGFR-3 IgG titers. Skin biopsy confirmed the presence of SFN in all patients by demonstrating decreased intraepidermal nerve fiber density. CONCLUSIONS: The presence of anti-TS-HDS and anti-FGFR-3 autoantibodies in patients with NCP with positive skin biopsy findings for SFN highlights the potential role of dysimmune SFN in the pathogenesis of this disease.

Interobserver and Intraobserver Agreements of the Detection of Demodex Infestation by in Vivo Confocal Microscopy.

Objectives: The purpose of the study was to determine interobserver and intraobserver agreement, repeatability, and intrasubject variation of the detection of Demodex infestation in eyelids of blepharitis patients using in vivo confocal microscopy (IVCM). Methods: Eighty-three eyes of 42 blepharitis patients were included in the study. All eyelids were evaluated from temporal to nasal with IVCM using section mode and 10 lashes with their follicles were imagined, and every image with suspicion of Demodex infestation was recorded. Two experienced and two inexperienced ophthalmologists were masked for the diagnosis and interpreted the IVCM images regarding the presence of Demodex infestation with a 3-week interval. Interobserver and intraobserver agreements were calculated with Cohen's kappa and its variant statistics between and within experienced observers and between inexperienced observers. Results: While average sensitivity for the diagnosis of demodicosis in IVCM images was 83.35% for experienced and 51.35% for inexperienced observers, the average positive predictive value was 88.6% for experienced observers and 91.05% for inexperienced ones. Interobserver agreement between experienced observers was moderate (κ = 0.529) and intraobserver agreements within experienced observers were perfect (κ = 0.918 for observer-1; κ = 0.958 for observer-2). Interobserver agreement between inexperienced observers was poor (κ = 0.162) and intraobserver agreements within inexperienced observers were fair (κ = 0.427 for observer-3; κ = 0.475 for observer-4). Conclusion: The sensitivity, interobserver and intraobserver agreements in IVCM image analysis for the detection of Demodex infestation were highly associated with the clinical experience on IVCM imaging. In the hands of an experienced clinician, IVCM could be reliable for the diagnosis of ocular demodicosis.

Acute Pancreatitis in Individuals with COVID-19: A Case Report and Critical Review of Literature.

Involvement of gastrointestinal tract has been reported in individuals diagnosed with COVID-19. Herein, we report a case of 65-year-old woman with type 2 diabetes mellitus, hypertension, and end-stage renal disease undergoing hemodialysis who was initially diagnosed with COVID-19 on a screening test. During the course of the disease, her respiratory symptoms remained mild; however, she developed acute pancreatitis leading to severe hypertension and hyperosmolar hyperglycemic state. During the hospitalization and treatment of acute pancreatitis, hyperglycemia, and hypertension, her condition improved and she was discharged in stable condition.

Concurrent ocular pain in patients with neurotrophic keratopathy.

PURPOSE: To illustrate that ocular pain may occur in patients with neurotrophic keratopathy (NK) that typically are thought to lack symptoms of discomfort, and that aa subset of these patients may also present with neuropathic corneal pain (NCP). METHOD: Retrospective Case series of 7 stage 1 NK patients who presented with concurrent ocular pain, as confirmed by clinical examination, proparacaine challenge test, and in vivo corneal confocal microscopy (IVCM). Records were assessed for results of ocular surface disease index (OSDI), pain on visual analog scale (VAS), ocular pain assessment survey (OPAS), best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS) score, and IVCM findings. IVCM findings were compared to that of 20 healthy reference controls. RESULTS: Mean age of patients was 63.7 ± 11.6 (range 44-76) years and 56.9 ± 8.6 (range 42-74) years in reference controls (p = 0.11). At presentation, ocular discomfort was 8.0 ± 1.3 (range 7-10) on VAS and mean OSDI scores were 72.26 ± 6.81 (range 62.50-79.54). Mean BCVA was 20/40, and mean CFS scores were 3.43 ± 0.79 (range 2-4) on the Oxford scale. IVCM analysis showed significant decrease in mean total, main and branch nerve densities in ranges consistent with NK as compared to normal controls (p < 0.001 for all), increased dendritiform cell density in three patients (p < 0.001), and the presence of microneuromas in six of the patients. CONCLUSION: Patients with NK are thought to present with hypoesthesia. However, nerve damage and inflammation, which play a role in the development of NK may result in the development of chronic ocular pain, such as NCP, resulting in potential underdiagnosis of either disease.

A novel investigation method for axonal damage in neuromyelitis optica spectrum disorder: In vivo corneal confocal microscopy.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disorder that damages optic nerves, brainstem, and spinal cord. In vivo corneal confocal microscopy (IVCM) is a noninvasive technique that provides corneal images with dendritic cells (DCs) and corneal subbasal nerve plexus (SBP), which arises from the trigeminal nerve. OBJECTIVE: We investigated corneal SBP changes in NMOSD and proposed IVCM as a potential new disease severity biomarker for NMOSD. METHODS: Seventeen age-sex matched NMOSD patients and 19 healthy participants underwent complete neurologic and ophthalmologic examinations. The duration of disease, first symptom, presence of optic neuritis attack, antibody status, Expanded Disability Status Scale(EDSS) score and disease severity score(DSS) were recorded. Retinal nerve fibre layer (RNFL) thickness was measured with optical coherence tomography, and corneal SBP images were taken with IVCM. RESULTS: NMOSD patients had significantly reduced corneal nerve fibre lenght-density and corneal nerve branch lenght-density compared with controls, while DC density was increased. NMOSD patients also showed significantly reduced RNFL thickness compared with controls. EDSS,DSS levels were inversely correlated with IVCM parameters. CONCLUSION: We observed significant corneal nerve fibre loss in NMOSD patients in relation to disease severity. IVCM can be a candidate noninvasive imaging method for axonal damage assessment in NMOSD that warrants further investigation.

Topical Adoptive Transfer of Plasmacytoid Dendritic Cells for Corneal Wound Healing.

Plasmacytoid dendritic cells (pDCs) are crucial for corneal homeostasis through secretion of various anti-angiogenic molecules and growth factors. Due to its avascular nature, only a limited number of adoptively transferred cells home to the cornea, when administered systemically. In addition, local adoptive transfer of cells poses several challenges and the clinical application of commonly used techniques is limited. Herein, we detail a novel approach for local adoptive transfer of pDCs to the cornea for the treatment of corneal wounds. This approach utilizes a commonly used fibrin sealant as a means of transferring previously isolated cells locally on the cornea. The technique is simple, reproducible, and is accompanied with successful transfer and integration of a substantial number of the cells to the cornea. Application of this approach to transfer pDCs promotes corneal wound healing. Furthermore, this technique can be applied for adoptive transfer of any cell of interest to the cornea.

Comparison of clinical characteristics of post-refractive surgery-related and post-herpetic neuropathic corneal pain.

PURPOSE: To compare the clinical characteristics and in vivo confocal microscopy (IVCM) findings of patients with neuropathic corneal pain (NCP) due to refractive surgery (RS-NCP) and herpetic eye disease (H-NCP) to controls. METHODS: Sixteen patients with RS-NCP and 7 patients with H-NCP, and 37 healthy reference age- and sex-matched healthy controls were included to the study. The medical records were reviewed for demographic features, detailed disease history, ocular surface disease index (OSDI), ocular pain assessment survey (OPAS) scores. IVCM images of patients were analyzed and compared to reference controls by two masked observers. RESULTS: The mean pain intensity score for the last 24 h (5.1 ± 2.4 vs. 3.9 ± 1.2; p = 0.27), last 2 weeks (6.1 ± 2.5 vs. 4.8 ± 2.3; p = 0.13) for RS-NCP vs. H-NCP respectively, and quality of life scores (p = 0.23) were similar in both groups. Quality of life, especially mood (p = 0.06) and enjoying life/relations to others (p = 0.10) were affected in both groups, but were not statistically significant between groups. The mean total nerve density was lower in RS-NCP (5,702.4 ± 4,599.0 µm/mm2) compared to their respective controls (26,422.8 ± 4,491.0; p < 0.001) and in the H-NCP group (2,149.5 ± 2,985.9) compared to their respective controls (22,948.8 ± 3,169.0; p < 0.001). Alterations in DC density were similar between all groups (38.3 ± 48.0 cells/mm2 in RS-NCP, 61.0 ± 76.9 in H-NCP, p = 0.95). CONCLUSION: Neuropathic corneal pain patients due to refractive surgery show similar clinical characteristics, pain levels, quality of life impact, and IVCM findings as patients with NCP due to herpetic eye disease.

Can Rotational Thromboelastometry be a New Predictive Tool for Retinal Vein Occlusion Development?

PURPOSE: To evaluate clotting dynamics by a new tool called rotational tromboelastometry (ROTEM) in retinal vein occlusion. MATERIALS AND METHODS: Thirty-six patients who were diagnosed with retinal vein occlusion and 43 age and sex matched healthy controls were included in this study. Diabetes and use of anticoagulant therapy were exclusion criteria. All study participants underwent detailed ophthalmologic and systemic medical examination, including blood pressure measurement, hemoglobin-hematocrit levels, platelet count, coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels. Peripheral blood samples were collected and analyzed with ROTEM Coagulation Analyzer (Tem International, Munich, Germany). RESULTS: The RVO patients and controls did not differ with respect to age, sex, hemoglobin, hematocrit, platelet numbers, prothrombin time, activated partial thromboplastin time, fibrinogen levels, D-dimer levels, and glucose levels. When extrinsic thromboelastometry results were analyzed, RVO patients showed a significantly decreased clotting time (76.5 ± 15.0 vs. 95.0 ± 21 s, respectively; p = 0.01) and clot formation time (83.3 ± 22 vs. 99.7 ± 24s; p = 0.01) as compared with healthy controls. Other ROTEM parameters did now show any difference between two groups. CONCLUSION: Patients with retinal vein occlusion showed faster clotting time and shorter clotting formation time as compared with healthy controls. ROTEM detects the altered clotting dynamics and may be a useful tool to elucidate the disease pathophysiology. Further studies are needed to investigate if it can be used as a screening test for individuals who are under risk to develop RVO or as a first step test to evaluate hypercoagulable state in RVO.

Severe Dry Eye in CD25 Deficiency Syndrome.

CD25 deficiency (Interleukin-2 receptor alpha deficiency) is a rare subtype of combined B- and T-cell immunodeficiency. Recurrent infections and lymphocyte infiltration of multiple tissues are the main clinical presentations. Only four patients have been reported in whom ophthalmological findings were not described. In this article, ocular findings of CD25 deficiency in a 12-year-old child are highlighted.

Comparison of Efficacy of Two Different Topical 0.05% Cyclosporine A Formulations in the Treatment of Adenoviral Keratoconjunctivitis-Related Subepithelial Infiltrates.

Subepithelial infiltrates secondary to adenoviral keratoconjunctivitis may persist for years and cause blurred vision, halos, glare, and photophobia. These infiltrates arise from immune reaction against the virus, and few studies have reported topical cyclosporine A to be effective in the treatment of subepithelial infiltrates. Herein, we describe a patient with adenoviral keratoconjunctivitis-related subepithelial infiltrates who did not respond to treatment with a new topical cyclosporine A emulsion prepared with castor oil (Depores 0.05%; Deva Ilaç, Kocaeli, Turkey), while the FDA-approved nanoemulsion formulation provided improvement in symptoms and reduced the inflammatory reaction (Restasis 0.05%; Allergan, Irvine, Calif., USA).

Pediatric Corneal Collagen Cross-Linking: Long-Term Follow-Up of Visual, Refractive, and Topographic Outcomes.

PURPOSE: To evaluate the long-term visual, refractive, and topographic outcomes of corneal collagen cross-linking (CXL) in the management of pediatric keratoconus. METHODS: Forty eyes of 40 consecutive patients with progressive keratoconus aged below 19 years were enrolled in this prospective study. All patient eyes underwent CXL with the standard (Dresden) protocol. Uncorrected distance visual acuity, best spectacle-corrected distance visual acuity, manifest refraction, slit-lamp biomicroscopy, corneal topography, corneal aberrometry, and endothelial cell counts were evaluated at baseline and at all postoperative follow-up examinations until month 48. RESULTS: Mean age of patients was 15.2 ± 1.9 years (10-18 years). Follow-up was 4 years. The mean improvements in uncorrected distance visual acuity (from 0.9 ± 0.3 logMAR to 0.5 ± 0.3 logMAR) and best spectacle-corrected distance visual acuity (from 0.4 ± 0.2 logMAR to 0.1 ± 0.1 logMAR) were statistically significant at month 48 (P = 0.0001). The mean Kmax decreased from 58.4 ± 5.5 D at baseline to 57.0 ± 5.3 D at month 48 (P = 0.04). Significant improvements in topographic and elevation indices and corneal aberrations were also noted after postoperative month 6. There was no change in the mean endothelial cell density (P > 0.05), and there was no progression or sight-threatening complication in any patient eye. CONCLUSIONS: Corneal CXL seems to be safe and effective in halting the progression of keratoconus in pediatric patients at 4-year follow-up. In addition, the procedure provides improvements in visual, refractive, topographic, and corneal aberrometric measurements.

Ocular Tuberculosis with Progressive Unilateral Corneal Melting.

OBJECTIVES: In this case report, we present a patient with ocular tuberculosis presenting with progressive unilateral corneal melting. PATIENT: A 47-year-old female was admitted with melting at the inferior half of the peripheral cornea and inferior subconjunctival nodules. Biopsy material of the nodules was negative for tuberculosis bacillus. However, polymerase chain reaction of the biopsy sample revealed the DNA of the bacillus, and the diagnosis was confirmed. CONCLUSION: In endemic areas, ocular tuberculosis should be kept in mind in the differential diagnosis of patients with chronic and atypical corneal involvement.