Retinal morphological and functional response to Idebenone therapy in Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to optic atrophy due to degeneration of the retinal ganglion cell. A curative treatment is not available at the moment, but a new antioxidant drug, Idebenone, is expected to reduce the progression of the disorder. Two male patients, genetically confirmed with LHON, were clinically, morphologically, and electrophysiologically evaluated, before and three, six, nine and 12 months after starting the treatment. The patient with 3460G>A mutation in mitochondrially-encoded nicotinamide adenine dinucleotide, reduced form (NADH):ubiquinone oxidoreductase core subunit (mtND)1 gene showed an improvement in visual acuity, visual field, and visual evoked potentials with no effect on morphological examinations, while the patient with 11778G>A mutation in mtND4 gene showed no functional, nor morphological recovery after one year of treatment. This study demonstrates that Idebenone, depending on the genetic profile of the disease, may be effective in functional improvement in patients with LHON.

Behavior pattern of early-stage ocular surface squamous cell carcinoma in non-HIV patients.

Ocular surface squamous neoplasia (OSSN) is a malignant or dysplastic lesion that has its origins in the epithelial cells at the ocular surface. The structures from which these lesions can arise are the conjunctiva, the limbus, and the cornea. Our study was conducted on a group of seven patients with ocular surface squamous cell carcinoma (SCC). Histopathologically diagnosed SCCs were then assessed as well, moderately and poorly differentiated, depending on which area of differentiation dominated in Hematoxylin-Eosin staining. For the immunohistochemical analysis, the following antibodies (markers) were used: Ki67, p53 and B-cell lymphoma 2 (Bcl-2), E-cadherin, and vascular endothelial growth factor (VEGF). Our study group was composed of seven cases of SCCs of the ocular surface. Three were below in T1 American Joint Committee on Cancer (AJCC) stage, two cases were in T2 AJCC stage, and two cases were in T3 AJCC stage. None of our cases were T4, N1 or M1 AJCC tumors. Four of the cases were histopathologically moderately differentiated SCCs of the ocular surface and three were poorly differentiated SCCs. None of the seven patients present human immunodeficiency virus (HIV) infection. P53 immunostaining was strongly present in our study. Bcl-2 overexpression is not a fact that our study highlights. The expression of Ki67 proliferation marker was low in our study. Our study on ocular surface SCC reveals negative assessment of VEGF immunostaining. E-cadherin expression in our study was positive. Ocular surface SCCs are slow growing tumors, with very low metastasis potential, when HIV-infection is not present.

Posterior vitreous detachment and macular anatomical changes - a tomographic-electroretinographic study.

AIM: Posterior vitreous detachment (PVD) is a physiological phenomenon due to aging characterized by separation of the vitreous cortex from the retina and may induce a variety of pathological events at the vitreoretinal junction. The aim of this study is to highlight in vivo anatomical and functional changes in early stages of PVD allowing the correct treatment. MATERIAL AND METHODS: Non-consecutive case series; optical coherence tomography (OCT) relies on analyzing the reflectivity of coherent light from different anatomical interfaces within posterior vitreous and retinal histological layers, thus acquiring transverse sections through vitreoretinal interface, sensory retina, retinal pigment epithelium and choroid. Modern techniques using Fourier spectral analysis of the reflected light enhance axial resolution to 5-10 µm, almost matching classic histological sections. Integrating these sections, OCT can reconstruct three-dimensional tissue anatomy. Full-field electroretinogram (ERG) evaluates the function of the entire retina evoked by a flash light. RESULTS: Imaging of the vitreoretinal interface with OCT allowed staging PVD and correctly diagnosing its secondary pathologies: cystoid macular edema, vitreomacular traction syndrome, epiretinal membrane, macular pucker, macular hole, macular pseudohole, lamellar macular hole. The cone response of full-field ERG is a marker of retinal damage in macular pathology due to PVD. CONCLUSIONS: Correct understanding of vitreoretinal anatomic and functional changes due to posterior vitreous detachment is essential for a proper diagnosis and treatment.

Clinical and histopathological aspects in two cases of ligneous conjunctivitis.

Ligneous conjunctivitis represents a very rare form of chronic membranous conjunctivitis, with unknown etiology; less than 200 cases have been reported in the literature, most of them in infants and children. After 40 years, this condition appears in exceptional circumstances. We present, in this study, two patients (of 55 and 64 years old) with very severe forms of ligneous conjunctivitis, certified by histopathological examination, one of them being previously diagnosed with Lyell's syndrome. The histological examination in ligneous conjunctivitis is important for diagnostic but also to elucidate the etiopathological context. A discontinued hyperplastic conjunctiva with numerous nuclear abnormalities and marked intra- and inter-cellular edema was characteristic for both cases. The epithelium layer presents large area of extension into the connective tissue, in the form of cysts and gland-like structures, or creating deep epithelial lacunas, with goblet cells. The connective subepithelial tissue presents diffuse inflammatory infiltration, with round cells, especially near vessels. Inside the conjunctival tissue, big hyaline areas with rare cellularity are detected. The amorphous deposits containing fibrillar material are also present. At the level of pseudo-membranes, we recorded a massive exudation of fibrin with an inflammatory cellular infiltration, and large areas containing an amorphous eosinophilic hyaline material. The association of ligneous conjunctivitis with Lyell's syndrome in one of our patients suggests its immuno-allergic etiology.

Impression conjunctival cytology in sicca syndrome - correlations between clinical and histological findings related to dry eye severity.

Keratoconjunctivitis sicca represents a progressive deterioration of ocular surface produced by a deficient secretion of lachrymal film (quantitative disorder) or excessive tear evaporation (qualitative disorder). The cytological analysis of conjunctival impression in 42 patients with dry eye syndrome established a strong correlation between the clinical grade of severity of disease and the grade of squamous metaplasia, including goblet cell loss. The cellular anomalies were represented by modifications of keratinization, epithelial cells' anisocytosis, anisochromia, the nuclear condensation and the cytoplasmic vacuolization. Pyknotic nuclei and anucleated cells were only seen in the most severe dry eye. The modifications in epithelial cells and conjunctival goblet cells reveal cellular sufferance, with an evident parallelism between these anomalies and clinico-functional signs in dry eye. Conjunctival impression provides an easy and quick identification of the lachrymal film alterations with high specificity and sensitivity, giving valuable information about the qualitative disorder.

Assessment of VEGF and EGFR in the study of angiogenesis of eyelid carcinomas.

A tumor represents an abnormal tissue growth that can arise from any ocular structure, such as eyelids, muscles or the optic nerve. At the eyelids, there are two main tumor types: basal cell carcinoma and squamous cell carcinoma. Angiogenesis plays a crucial role in growth, invasion and metastasis processes of any tumor. It is well known the fact that without new vessels formation tumors cannot exceed 1-2 mm diameter. Immunohistochemical analysis has been performed on 43 cases of primary carcinomas of the eyelid, diagnosed between 2010 and 2014 in the Laboratory of Pathological Anatomy of the University Emergency County Hospital of Craiova, Romania. Biological material was represented by surgical resection samples, coming from the Clinic of Ophthalmology the anteriorly named Hospital. Within the immunohistochemical study, we have evaluated epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression in a group of 43 cutaneous carcinomas of the eyelid, depending on the type and differentiation grade of the tumor. Of the 43 samples, 23 came from patients with eyelid basal cell carcinoma and 20 came from patients with eyelid squamous cell carcinoma. In our study, EGFR and VEGF immunoexpression was superior for squamous cell carcinomas, compared to basal cell carcinomas, fact that was statistically significant. Regarding squamous cell carcinomas, the immunoexpression of these two markers was superior in moderate÷poor differentiated forms, compared to well differentiated forms, fact that was statistically significant. The markers used in this study were found to be associated with the acquisition of aggression and angiogenic phenotypes by analyzed carcinomas.

Histological and immunohistochemical study of the eyelid basal cell carcinomas.

The eyelids represent a frequent site for numerous malignant tumors, which generally present subtle symptoms or can imitate benignant tumors. Our study was carried on 80 patients, 48 males and 32 females aged between 48 and 92 years. The patients were hospitalized in the Ophthalmology Clinic of the Emergency County Hospital of Craiova, Romania. The study was conducted over five years, between 2010 and 2014. Our study included 80 basal cell carcinomas of the eyelids, of which 48 (60%) were nodular basal cell carcinomas, 15 (18.75%) were adenoid basal cell carcinomas, 10 (12.5%) were cystic and seven (8.75%) were morpheaform basal cell carcinoma. Our study showed a moderate expression of bcl-2 marker in the nodular type of basal cell carcinoma and a high expression in the other histopathological types, thus inducing an increased malignancy comparing to the nodular type. E-cadherin was absent in nodular, cystic and adenoid basal cell carcinomas and had a moderate expression in morpheaform basal cell carcinoma. Morpheaform and adenoid types presented 20% expression of Ki67 of the malignant cells nuclei, while the cystic type presented Ki67 expression in less than 10% of the malignant cells nuclei. Due to high morbidity and increasing incidence, basal cell carcinoma of the eyelid represents an important health issue nowadays.

Fulminant evolution in one case of choroidal melanoma - predictive factors for general metastasis.

Comparing with other malignant tumors, uveal melanomas determine tardive general spreading. Even in the absence of local treatment, general metastasis is less than 20%, in the first five years, many factors being involved. This paper present a particular case of choroid melanoma with very unusual and unpredictable evolution of the disease; the high growth of tumor size (in only half year the tumor almost doubled up dimensions), was associated with hepatic metastasis developed in only several months. In our opinion, this case, presenting a very atypical evolution may contribute to increase our knowledge of the mechanisms underlying metastasis and the identification of reliable progression parameters as prognostic markers in primary uveal melanoma. Several histological characteristics and demographic factors have been associated with disease evolution: presence of retinal neovessels and neovascular glaucoma, rapid increasing tumor thickness, scleral invasion, epithelioid cell types with large nucleoli, lymphocytic infiltration, and vascular pattern with networks of loops. Sclera invasion is uncommon in choroid tumors, but it is associated with an unfavorable bad prognosis, giving a great propensity to metastasize and to affect the liver. The median survival following diagnosis of hepatic metastasis is only several months.

Oral mucosa self-graft in a patient with invasive conjunctival melanoma: a case report.

Conjunctival melanoma is a rare tumor, while malignant melanoma of the uveal tract is the most common primary intraocular tumor in adults. The authors highlighted the case of a 68-year-old male patient presented in June 2011 in the Ophthalmology Clinic of the Emergency County Hospital of Craiova, Romania, accusing foreign body sensation and the appearance of a tumor in the lower fornix of his right eye. The patient was clinically and paraclinically investigated, and clinically diagnosed with de novo malignant melanoma. The tumor was surgically excised and the lower fornix reconstructed with oral mucosa self-graft. Histopathological diagnosis was de novo, invasive, ulcerated malignant melanoma of the conjunctiva. Ki-67 immunohistochemical staining was also performed. After surgery, the patient was sent to the Oncology Department for specific treatment. Despite the histological poor prognosis factors present in our patient, two years after surgery and chemotherapy, the patient had no clinical sign of local or distance recurrent disease. Continuous ophthalmologic and oncological surveillance is necessary.