Safety and efficacy of sodium cromoglycate-fluorometholone fixed combination eye drops in allergic conjunctivitis.

PURPOSE: This study aimed to assess the efficacy and safety of sodium cromoglycate with fluorometholone in patients with allergic conjunctivitis. METHODS: We conducted a single-arm phase IV open-label trial where fifty patients who received the eye drops were followed for 4 weeks. Treatment efficacy was assessed using the ocular itching score, conjunctival assessment score, total symptom and sign (TSS) score, and Visual Analog Scale (VAS). RESULTS: Patients who received sodium cromoglycate-fluorometholone eye drops experienced significant improvements in their ocular itching score (mean difference [MD]: 1.14, P < 0.001) and conjunctival redness score (MD: 1.18, P < 0.001). Statistically significant improvements in TSS and VAS were achieved in 78% of the patients reporting no conjunctivitis by the end of the study. The overall therapeutic response to the drug was as follows: 16% improved and 84% much improved. No serious adverse events were reported. CONCLUSION: Sodium cromoglycate with fluorometholone eye drops achieved 100% therapeutic response among patients with allergic conjunctivitis. The eye drops improve the ocular itching, and conjunctival irritation without serious adverse events. This combination appears effective and tolerable for treatment of allergic conjunctivitis.

Posterior Embryotoxon Revisited: An Immunohistologic Study.

PURPOSE: This series describes the immunopathologic features of posterior embryotoxon (PE) and demonstrates that it is not an anterior displaced Schwalbe's line as commonly described, but a peripheral corneal stromal nub variable in location with abnormal extracellular matrix. DESIGN: Case series. PARTICIPANTS: Archived specimens from patients with PE. METHODS: Sections from archived formalin-fixed, paraffin-embedded specimens (n = 9; 7 autopsy and 2 trabeculectomy specimens) were examined by light microscopy. Immunohistochemistry was performed on 5 specimens to characterize the extracellular matrix composition of PE. RESULTS: Posterior embryotoxon appeared as nubs of whorled collagen extending from the corneal stroma, lined in some instances, by Descemet membrane. These nubs were located anterior to Schwalbe's line (n = 4), posteriorly (n = 1), partially embedded in the trabecular meshwork (n = 1), or at Schwalbe's line (n = 2). Qualitatively, collagen I labeling of the PE stroma was similar or weaker than the corneal stroma, whereas collagen III staining was focal and slightly more intense compared with the corneal stroma. Lumican and keratan sulfate staining was similar or less intense in PE compared with the corneal stroma. MAIN OUTCOME MEASURES: Identify location of PE and its immunohistochemical features. CONCLUSIONS: In contrast to the widely accepted definition of PE as a prominent, anteriorly displaced Schwalbe line, histologic evidence suggests that it is a direct extension of the corneal stroma with variable locations that may displace the attenuated Descemet membrane when located anterior to or at Schwalbe's line. Immunohistochemical examination revealed that the composition of PE's extracellular matrix was similar to corneal stroma but with some variability in staining intensity.

Cataract surgery training using surgical simulators and wet-labs: Course description and literature review.

Cataract surgery is the most common surgery to face the ophthalmology training resident. To facilitate achieving surgical competency and reduce complication rates, wet laboratories and surgical simulators are used in surgical disciplines worldwide. We developed a simulator and wet-lab course that aims to build the microsurgery skills of trainees and improve safety during real surgical procedures. Herewith, we describe the standardized hands-on course that incorporates these tools for advanced training. Additionally, we review the literature on wet-lab and surgical simulators in ophthalmology, focusing on their importance in training centers. The course is offered four times per year since it started in December 2015, and t total of 88 trainees participated to date. Feedback received from the trainees' supervising surgeons showed that this course addresses a major training challenge, and that a permanent version of this course should be established at each training center. We suggest incorporating fixed wet-lab and surgical simulator competencies in ophthalmology training programs. Additionally, we recommend that residents be allowed to operate on real patients only after passing the course. We believe that these steps would foster ophthalmologists with advanced training, decrease their learning curve, and empower them to safely conduct cataract surgery with low complication rates.

Gene Expression Profile of Extracellular Matrix and Adhesion Molecules in the Human Normal Corneal Stroma.

PURPOSE: There is limited information on region-specific gene expression in the human corneal stroma. In this study, we aimed to investigate the expression profile of the extracellular matrix and adhesion molecules in the normal corneal stroma using laser capture microdissection (LCM) and molecular techniques. METHODS: Frozen sections of human cornea without ocular disease were used to isolate the central and peripheral corneal stromal keratocytes by LCM. RNA was extracted from LCM-captured tissues and the RT2 Profiler PCR Arrays were used to examine the expression profile of extracellular matrix and adhesion molecules in the central and peripheral stroma. Real-time quantitative PCR was used to quantify gene expression. Proteomic and western blotting (WB) analyses were performed to confirm gene expression at protein level. Function association network was generated via the web tools String and Cytoscape. RESULTS: The gene expression profiling demonstrated that 35 out of the 84 extracellular matrix and adhesion molecules represented in the array were expressed in stromal keratocytes. Among them, 24 genes were not previously described in the corneal stroma. Two genes were found more abundantly expressed in the central stroma than in the periphery: TGFBI, COL6A2 (p < 0.05). ADAMTS13 was detected only in the central stroma. Proteomics and WB analysis confirmed the expression of 10 genes. Functional analysis revealed that most identified genes were presented in a core cluster that had multiple and strong associations with other genes. CONCLUSION: This study identified genes not previously described in the corneal stroma, revealed regional differences in gene expression between central and peripheral stroma, and also detected some interesting candidate genes that may play important roles in corneal function. These observations serve as the foundation to further investigate the molecular and cellular mechanisms regulating the pathogenesis of regional corneal stromal disorders such as keratoconus.

Subepidermal Calcified Nodules of the Eyelid Differ in Children and Adults.

PURPOSE: Subepidermal calcified nodule of the eyelid is considered as one of the types of calcinosis cutis. It generally occurs in children, and is not known to be associated with systemic disease. The authors report histopathological and clinical findings in 14 cases of subepidermal calcified nodule of the eyelid, including 3 older patients with unique microscopic features. METHODS: Clinical records and pathological materials were critically reviewed in each case, including von kossa, CD3, CD20, and CD68 stains. RESULTS: The 14 cases presented clinically as nodular eyelid lesions. All were treated with surgical excision. The authors found 2 distinct histopathological patterns which correlated with the patients' age. In young patients, the authors observed multiple, small calcified bodies within the dermis surrounded by chronic inflammation and granulomatous foreign body reaction. On the other hand, in elderly patients, lesions were characterized by a single, large, well-demarcated amorphous calcified deposit surrounded by fibrous tissue, without chronic inflammation or foreign body reaction. One of these patients, a 70-year-old man, also suffered from gout. The presence of subepidermal calcified nodule was not documented as a preoperative diagnostic possibility in any of the cases. CONCLUSIONS: Subepidermal calcified nodule of the eyelid is a rare condition, but should be considered in any patient presenting with a painless white to yellowish colored nodule of the ocular adnexa, particularly during the teenage years. Clinicians and pathologists should be aware that this entity has a distinct appearance and could be associated with systemic conditions in elderly patients.

Altered gene expression in conjunctival squamous cell carcinoma.

Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface.

Corticosteroid-loaded biodegradable nanoparticles for prevention of corneal allograft rejection in rats.

Immunologic graft rejection is one of the main causes of short and long-term graft failure in corneal transplantation. Steroids are the most commonly used immunosuppressive agents for postoperative management and prevention of corneal graft rejection. However, steroids delivered in eye drops are rapidly cleared from the surface of the eye, so the required frequency of dosing for corneal graft rejection management can be as high as once every 2h. Additionally, these eye drops are often prescribed for daily use for 1 year or longer, which can result in poor patient compliance and steroid-related side effects. Here, we report a biodegradable nanoparticle system composed of Generally Regarded as Safe (GRAS) materials that can provide sustained release of corticosteroids to prevent corneal graft rejection following subconjunctival injection provided initially during transplant surgery. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing dexamethasone sodium phosphate (DSP) exhibited a size of 200 nm, 8 wt.% drug loading, and sustained drug release over 15 days in vitro under sink conditions. DSP-loaded nanoparticles provided sustained ocular drug levels for at least 7 days after subconjunctival administration in rats, and prevented corneal allograft rejection over the entire 9-week study when administered weekly. In contrast, control treatment groups that received weekly injections of either placebo nanoparticles, saline, or DSP in solution demonstrated corneal graft rejection accompanied by severe corneal edema, neovascularization and opacity that occurred in ≤ 4 weeks. Local controlled release of corticosteroids may reduce the rate of corneal graft rejection, perhaps especially in the days immediately following surgery when risk of rejection is highest and when typical steroid eye drop administration requirements are particularly onerous.

Identification of multiple DNA copy number alterations including frequent 8p11.22 amplification in conjunctival squamous cell carcinoma.

PURPOSE: Little is known about the molecular alterations that drive formation and growth of conjunctival squamous cell carcinoma (cSCC). We therefore sought to identify genetic changes that could be used as diagnostic markers or therapeutic targets. METHODS: The DNA extracted from 10 snap-frozen cSCC tumor specimens and 2 in situ carcinomas was analyzed using array-based comparative genomic hybridization (aCGH), and further examined with NanoString and quantitative PCR. RESULTS: The number of regions of DNA loss ranged from 1 to 23 per tumor, whereas gains and amplifications ranged from 1 to 15 per tumor. Most large regions of chromosomal gain and loss were confirmed by NanoString karyotype analysis. The commonest alteration was amplification of 8p11.22 in 9 tumors (75%), and quantitative PCR analysis revealed 100-fold or greater overexpression of ADAM3A mRNA from 8p11.22 locus. In addition, recurring losses were observed at 14q13.2 and 22q11.23, both lost in 5 (42%) of the 12 tumors, and at 12p13.31, lost in 4 (33%) of the 12 samples. Of the eight loci associated with the DNA damage repair syndrome xeroderma pigmentosum, three showed loss of at least one allele in our aCGH analysis, including XPA (9q22.33, one tumor), XPE/DDB2 (11p11.2, one tumor) and XPG/ERCC5 (13q33.1, three tumors). CONCLUSIONS: Conjunctival SCC contains a range of chromosomal alterations potentially important in tumor formation and growth. Amplification of 8p11.22 and overexpression of ADAM3A suggests a potential role for this protease. Our findings also suggest that defects in DNA repair loci are important in sporadic cSCC.

No increase in IgG4-positive plasma cells in limbal Rosai-Dorfman disease.

PURPOSE: Extranodal Rosai-Dorfman disease is a rare benign condition recently reported to sometimes show features of IgG4-related disease. The purpose of this study was to describe the corneal-limbal manifestation of the entity and to investigate whether numerous IgG4-positive plasma cells are associated with the disease at this site. METHODS: This is an interventional retrospective small case series. RESULTS: Two patients presenting with painless limbal mass lesions underwent total excisional biopsy with anterior lamellar keratoplasty for diagnostic and therapeutic purposes. Histopathologic evaluation of the specimens revealed inflammatory lesions containing atypical S100-immunoreactive histiocytes diagnostic of Rosai-Dorfman disease, but not an increase in the IgG4-positive plasma cells. Point mutations (V600E) in the BRAF oncogene were absent. CONCLUSIONS: Rosai-Dorfmann disease should be considered in the differential diagnosis of limbal mass lesions. Involvement at this site was not associated with BRAF mutation or IgG4 abnormalities in the cases examined.

Severe ocular injury and its management following self induced plant extracts: A case report.

INTRODUCTION: Homemade and folk remedies' use is widely practiced in under developed countries, of the used materials are plant extracts, lemon juice and some dried insect bodies. CASE PRESENTATION: We report a case of severe ocular injury and its management after self administered plants seeds in both the eyes of a 47-year-old man who had bilateral severe ocular damage after he put the seeds of a plant Lepidium Sativum (Rashad) in his eyes. He reported severe ocular pain and redness, conjunctival epithelial defect and symblepharon. A conjunctival biopsy was taken which turned out to be negative for the immunological staining studies for Ocular Cicatricial Pemphegoid (OCP). The patient's visual acuity improved from 20/40 before treatment to 20/25 after treatment with no further sequelae after 3 months follow-up. CONCLUSIONS: Self induced plant extracts can cause ocular complications. Public awareness is necessary to help in discouraging the use of these harmful plant extracts in human eyes.