This review describes a scheme for diagnosis of glaucoma in population based prevalence surveys. Cases are diagnosed on the grounds of both structural and functional evidence of glaucomatous optic neuropathy. The scheme also makes provision for diagnosing glaucoma in eyes with severe visual loss where formal field testing is impractical, and for blind eyes in which the optic disc cannot be seen because of media opacities.

https://bjo.bmj.com/content/bjophthalmol/86/2/238.full.pdf

The definition and classification of glaucoma in prevalence surveys

Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy, by transmission electron microscopy, or by using an immunohistochemical panel of endothelial cell markers (Factor VIII-related antigen, Ulex, CD31, CD34, and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in three-dimensional cultures containing Matrigel or dilute Type I collagen, without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye, highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions, even after the addition of conditioned medium from metastatic pattern-forming melanoma cells, soluble growth factors, or regimes of hypoxia. Highly invasive and metastatic human melanoma cells, but not poorly invasive melanoma cells, contracted and remodeled floating hydrated gels, providing a biomechanical explanation for the generation of microvessels in vitro. cDNA microarray analysis of highly invasive versus poorly invasive melanoma tumor cells confirmed a genetic reversion to a pluripotent embryonic-like genotype in the highly aggressive melanoma cells. These observations strongly suggest that aggressive melanoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis.

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Background Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes. We studied the use of autologous oral mucosal epithelial cells as a source of cells for the reconstruction of the corneal surface. Methods We harvested 3-by-3-mm specimens of oral mucosal tissue from four patients with bilateral total corneal stem-cell deficiencies. Tissue-engineered epithelial-cell sheets were fabricated ex vivo by culturing harvested cells for two weeks on temperature-responsive cell-culture surfaces with 3T3 feeder cells that had been treated with mitomycin C. After conjunctival fibrovascular tissue had been surgically removed from the ocular surfa...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa040455

Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium.

An Integrated Hypothesis That Considers Drusen as Biomarkers of Immune-Mediated Processes at the RPE-Bruch's Membrane Interface in Aging and Age-Related Macular Degeneration

https://oftalmologiarafaelcaiado.files.wordpress.com/2012/04/anchor-study.pdf

Ranibizumab versus Verteporfin Photodynamic Therapy for Neovascular Age-Related Macular Degeneration: Two-Year Results of the ANCHOR Study

Using optic disk photographs, qualitative morphologic characteristics of the optic nerve head were determined in 251 nonselected normal eyes and 308 eyes with chronic primary open-angle glaucoma. These characteristics were correlated to morphometric (both intra- and parapapillary) and perimetric data. The highest degree of accuracy in distinguishing normal from glaucomatous optic disks was found with the characteristics "localization of narrowest point of neuroretinal rim outside the temporal horizontal optic disk sector" (85.5%) and "changes in the parapapillary retinal nerve fiber layer" (87.9%). The signs "baring of circumlinear vessels," "baring of cilioretinal arteries," "epipapillary flame-shaped hemorrhages," and "bridging of the vessel trunk" were highly specific for glaucomatous optic nerve damage (94.4%-100%) and less sensitive (5.8%-25.3%). Bayonetlike vessel kinking," "prevalence of cupping nasal to the main vessel trunk," "baring of the lamina cribrosa pores," and "undermining of the cup border" were less useful in qualitative evaluation of the optic disk. The location of the central artery in relation to the central vein (nasal in 98.4%), prevalence of the cilioretinal arteries, and the total number of circumlinear vessels were not significantly correlated to changes associated with glaucoma and are therefore of no importance for optic disk evaluation in glaucoma.

Qualitative morphologische Charakteristika von Normal- und Glaukompapillen

Trephination in Penetrating Keratoplasty

Besides routine postoperative follow-up, the prophylaxis of complications in penetrating keratoplasty (PKP) includes special preoperative and intraoperative aspects. Preoperative prophylaxis consists of the therapy of systemic diseases and eyelid abnormalities, determining individual optimal graft size, avoiding PKP in cases of uncontrolled intraocular pressure, avoiding PKP in cases of acute corneal hydrops, pretreatment of vascularized cornea, amniotic membrane transplantation before PKP in cases of ulcerative keratitis, quality-controlled organ-cultured transplants, and preoperative counseling by the microsurgeon to ensure patient compliance. Intraoperative prophylaxis consists of controlled arterial hypotension and complete relaxation during general anesthesia and application of a Flieringa ring in aphakic vitrectomized eyes. Precautions for intraoperative prophylaxis of astigmatism must be followed. A measurable improvement seems to be possible using the technique of nonmechanical trephination of patient and donor from the epithelial side using the excimer laser but not the femtosecond laser. Graft size should be adjusted individually (“as large as possible, as small as necessary”). Limbal centration should be preferred over pupil centration (especially in keratoconus). In addition to the situation-specific diagnosis and preoperative planning, the critical selection of the donor tissue, and the minimally invasive microsurgical technique, it is especially the indication-dependent close-meshed follow-up which plays an important role in the long-term success of penetrating keratoplasty. In the follow-up process, the repeated emphatic sensitization of the patient to alarming subjective symptoms and the informed involvement of the ophthalmologist in private practice providing the follow-up treatment must be considered of crucial importance. “Treat them and street them” is certainly not the motto to follow!

The Penetrating Keratoplasty (PKP): A Century of Success

Background Epithelial tumors of the epibulbar conjunctiva are rare in northern Europe. There are no reliable clinical criteria to predict the histological nature of the lesion. Even histologically proven malignant tumors typically do not show ocular invasion or metastasis. Patients and methods From 1980 to 1993, 112 epithelial epibulbar tumors were classified in our ophthalmopathological laboratory. Surgical management of 50 papillomas (mean age 46±18 years, 58% males), 49 conjunctival/corneal intraepithelial neoplasias (CIN) (28 mild, 21 severe) and 12 squamous cell carcinomas (mean age 63±13 years, 69% males) included excisional biopsy (61%), with additional lamellar keratectomy (14%), epithelial abrasion (10%), cauterisation (3%), cryotherapy (2%), excimer laser ablation (2%). Other management regimes were lamellar keratoplasty (2%), penetrating keratoplasty (2%), epithelial abrasion (2%). One eye with intraocular invasion of a mucoepidermoid carcinoma was enucleated. Results Fifty five per cent of the papillomas were located at the caruncle or semilunar fold. Seventy eight percent of the papillomas had a pedunculated appearence. Two lesions involved the epibulbar conjunctiva as well as the opposite tarsal conjunctiva (kissing papilloma). Eighty eight percent of CIN/carcinoma were located at the limbus. The clinical differential diagnoses of ClN/carcinoma were squamous cell carcinoma (26%), papilloma (18%), leukoplakia (10%), pinguecula/pterygium (10%), dysplasia (8%), malignant melanoma (5% ), trachoma (3%), chronic keratoconjunctivitis with corneal pannus (2%), granuloma (2%), non-pigmented naevus (2%). After a mean follow-up of 6.3±3.5 years, 13% of the papillomas showed a local recurrence. After a mean follow-up of 4.8±3.7 years, there were 30% local recurrences of CIN/carcinoma (50% each in severe CIN and carcinoma, 9% in mild C1N). But there was no recurrence of CIN/carcinoma in patients who had received a complete tumor resection initially. If the surgical margins were involved, there was a 64% recurrence rate (80% each in severe CIN and carcinoma). Thirteen per cent of the patients with CIN/carcinoma showed an additional malignant tumor elsewhere in the body. Conclusions Local recurrences after excision of CIN/carcinoma did occur only if the surgical margins where involved, and most often within the first year following surgery. Dedifferentiation of epithelial tumors in recurrences was not observed. The diagnosis of CIN/carcinoma of the conjunctiva requires the exclusion of an additional extraocular neoplasia. Histopathological classification and assessment of resection margins of epibulbar tumors is indispensable, especially in view of the more aggressive treatment necessary in mucoepidermoid carcinomas.

Differentialdiagnose und Prognose bei 112 exzidierten epibulbären epithelialen Tumoren

History An 8-year-old boy underwent bilateral repeat trabe- culectomies with large iridectomies at age 4 and 5 and cy- clocryocoagulation of the right eye at age seven for glaucoma. Findings The first examination in our department revealed a visual acuity of OD light perception, OS 0.2. The right eye was exotropic and hypotropic. The intraocular pressure was 30 mm Hg in both eyes. The corneal diameters were OD 9.0 x 7.0 and OS 8.5 x 6.5 mm, while the axial length was OD 25.3 and OS 23.6 mm. Both eyes had slightly prominent filter blebs with uveal incarceration. The chamber angles were open in both eyes and partly covered with uveal tissue, the E/P ratio was OD 1.0, OS 0.9. Extraocular changes were: dysplastic teeth, dental ena- mel hypoplasia, thickened jaw, small nose with pronounced nose bridge. Both hands showed shortening of the metacarpals and of the IVth digits as compared to the IInd and IIIrd digits. Syn- dactylic digits IV and V had been surgically separated earlier. Diagnosis Our diagnosis was juvenile open-angle glaucoma in oculo-dento-digital dysplasia. Therapy After trabeculotomy and cyclocryocoagulation IOP remained around 10 mm Hg. Conclusions Despite small corneal diameters, congenital glaucoma needs to be ruled out early in patients with oculo-dento-digital dysplasia. These patients should be treated in close cooperation with pediatric neurologists, orthopedic sur- geons, dentists and otorhinolaryngologists.

Gottfried O. H. Naumann

Papers

Qualitative morphologische Charakteristika von Normal- und Glaukompapillen

Trephination in Penetrating Keratoplasty

The Penetrating Keratoplasty (PKP): A Century of Success

Differentialdiagnose und Prognose bei 112 exzidierten epibulbären epithelialen Tumoren

[Juvenile open angle glaucoma with microcornea in oculo-dento-digital dysplasia (Meyer-Schwickerath-Weyers syndrome)].