Human skin consists of a stratified, cellular epidermis and an underlying dermis of connective tissue [1–5]. The dermal–epidermal junction is undulating in section; ridges of the epidermis, known as rete ridges, project into the dermis. The junction provides mechanical support for the epidermis and acts as a partial barrier against exchange of cells and large molecules. Below the dermis is a fatty layer, the panniculus adiposus, usually designated as ‘subcutaneous’. This is separated from the rest of the body by a vestigial layer of striated muscle, the panniculus carnosus. There are two main kinds of human skin. Glabrous skin (non-hairy skin), found on the palms and soles, is grooved on its surface by continuously alternating ridges and sulci, in individually unique configurations known as dermatoglyphics. It is characterized by a thick epidermis divided into several well-marked layers, including a compact stratum corneum, by the presence of encapsulated sense organs within the dermis, and by a lack of hair follicles and sebaceous glands. Hair-bearing skin (Fig. 3.1), on the other hand, has both hair follicles and sebaceous glands but lacks encapsulated sense organs. There is also wide variation between different body sites. For example, the scalp with its large hair follicles may be contrasted with the forehead, which has only small vellus-producing follicles, albeit associated with large sebaceous glands. The axilla is notable because it has apocrine glands in addition to the eccrine sweat glands, which are found throughout the body. Regional variation is further considered below. Chapter 3

Anatomy and Organization of Human Skin

This article discusses ocular surface squamous neoplasia, a spectrum of malignancy that includes intraepithelial dysplasia, carcinoma in situ of the conjunctiva and cornea, and invasive squamous cell carcinoma.

https://www.ophthalmology.theclinics.com/article/S0896-1549(04)00118-X/pdf

Ocular surface squamous neoplasia.

Even though ocular surface squamous neoplasia (OSSN) has been recognized for well over a century, the past decade has witnessed advances that have helped rewrite many of the paradigms for the diagnosis and management of these lesions. OSSN occurs predominantly in the elderly for whom they are the third most common oculoorbital tumors after melanoma and lymphoma. In addition to advanced age and male sex, other major risk factors linked to its pathogenesis are ultraviolet light, cigarette smoking, and the human papilloma virus. Although the latter has been linked to OSSN for nearly 4 decades, its identification and role in the pathogenesis of these tumors has been elucidated recently and is addressed in detail in this review. Newer techniques of impression cytology represent a noninvasive and reliable method of diagnosing OSSN and monitoring treated cases. The efficacy of chemotherapeutic agents such as mitomycin C and 5-fluorouracil have been proven in the recent past, making them a clear alternative to the time-tested treatment of surgical excision and cryotherapy. Early reports on the efficacy of topical Iterferon alpha 2b indicate significant promise in providing another alternative for the treatment of some of these neoplasms. These advances thus represent a minimally invasive and highly successful approach to the diagnosis and treatment of OSSN.

Ocular surface squamous neoplasia: a review.

The prospective intraoperative and perioperative ophthalmic imaging with optical CoherEncE TomogRaphy (PIONEER) study: 2-year results

Optical coherence tomography (OCT) has become one of the most successful optical technologies implemented in medicine and clinical practice mostly due to the possibility of non-invasive and non-contact imaging by detecting back-scattered light. OCT has gone through a tremendous development over the past 25 years. From its initial inception in 1991 [Science254, 1178 (1991)] it has become an indispensable medical imaging technology in ophthalmology. Also in fields like cardiology and gastro-enterology the technology is envisioned to become a standard of care. A key contributor to the success of OCT has been the sensitivity and speed advantage offered by Fourier domain OCT. In this review paper the development of FD-OCT will be revisited, providing a single comprehensive framework to derive the sensitivity advantage of both SD- and SS-OCT. We point out the key aspects of the physics and the technology that has enabled a more than 2 orders of magnitude increase in sensitivity, and as a consequence an increase in the imaging speed without loss of image quality. This speed increase provided a paradigm shift from point sampling to comprehensive 3D in vivo imaging, whose clinical impact is still actively explored by a large number of researchers worldwide.

Twenty-five years of optical coherence tomography: the paradigm shift in sensitivity and speed provided by Fourier domain OCT [Invited]

Perilesional and topical interferon alfa-2b for conjunctival and corneal neoplasia

Purpose To identify if recently described LOXL1 (lysyl oxidase-like 1) polymorphisms are associated with pseudoexfoliation glaucoma (XFG) in a United States (U.S.) Caucasian patient population. Methods Individuals with XFG were identified using standard clinical examination techniques. TaqMan allelic discrimination assays were used to genotype 13 single nucleotide polymorphisms (SNPs) that tag LOXL1 in Caucasian individuals. The coding region of exon 1 that includes the previously associated SNP, rs1048661, was sequenced. Allele and genotype frequencies were compared between cases and unrelated controls. Results Fifty affected individuals and 235 control individuals were recruited into this study. We replicated the previously reported association of three SNPs (rs1048661, rs2165241, and rs3825942) in our independent XFG population (single SNP p-values were 0.001-0.02). The risk alleles at these three and several other intragenic SNPs are part of an extended XFG-associated LOXL1 haplotype with a frequency of 32.0% in XFG patients and 21.6% in controls. Conclusions We have performed an analysis of LOXL1 and XFG in a United States patient population and have confirmed the strong association previously reported for Icelandic and Swedish samples. However, due to the high frequency of risk alleles in non-XFG individuals, this association should not form the basis of a diagnostic test for XFG. It is likely that additional genetic or environmental factors modulate the penetrance of LOXL1 susceptibility alleles.

/pdf/analysis-of-loxl1-polymorphisms-in-a-united-states-4m57ll9x64.pdf

Analysis of LOXL1 polymorphisms in a United States population with pseudoexfoliation glaucoma.

Purpose The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from preclinical testing into human intraoperative imaging. Methods Before human imaging, surgical conditions were fully simulated for extensive preclinical MIOCT evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board-approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. Results Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The preclinical evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. Conclusion This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.

/pdf/preclinical-evaluation-and-intraoperative-human-retinal-89j6mt8tfu.pdf

Preclinical evaluation and intraoperative human retinal imaging with a high-resolution microscope-integrated spectral domain optical coherence tomography device.

Primary open-angle glaucoma is the second leading cause of blindness in the United States and is commonly associated with elevated intraocular pressure (IOP) resulting from diminished aqueous humor (AH) drainage through the trabecular pathway. Developing effective therapies for increased IOP in glaucoma patients requires identification and characterization of molecular mechanisms that regulate IOP and AH outflow. This study describes the identification and role of autotaxin (ATX), a secretory protein and a major source for extracellular lysophosphatidic acid (LPA), in regulation of IOP in a rabbit model. Quantitative proteomics analysis identified ATX as an abundant protein in both human AH derived from non-glaucoma subjects and in AH from different animal species. The lysophospholipase D (LysoPLD) activity of ATX was found to be significantly elevated (by ∼1.8 fold; n = 20) in AH derived from human primary open angle glaucoma patients as compared to AH derived from age-matched cataract control patients. Immunoblotting analysis of conditioned media derived from primary cultures of human trabecular meshwork (HTM) cells has confirmed secretion of ATX and the ability of cyclic mechanical stretch of TM cells to increase the levels of secreted ATX. Topical application of a small molecular chemical inhibitor of ATX (S32826), which inhibited AH LysoPLD activity in vitro (by >90%), led to a dose-dependent and significant decrease of IOP in Dutch-Belted rabbits. Single intracameral injection of S32826 (∼2 µM) led to significant reduction of IOP in rabbits, with the ocular hypotensive response lasting for more than 48 hrs. Suppression of ATX expression in HTM cells using small-interfering RNA (siRNA) caused a decrease in actin stress fibers and myosin light chain phosphorylation. Collectively, these observations indicate that the ATX-LPA axis represents a potential therapeutic target for lowering IOP in glaucoma patients.

/pdf/autotaxin-lysophosphatidic-acid-axis-is-a-novel-molecular-2c49k3fkdy.pdf

Robin Vann

Papers

Perilesional and topical interferon alfa-2b for conjunctival and corneal neoplasia

Analysis of LOXL1 polymorphisms in a United States population with pseudoexfoliation glaucoma.

Preclinical evaluation and intraoperative human retinal imaging with a high-resolution microscope-integrated spectral domain optical coherence tomography device.

Autotaxin-lysophosphatidic acid axis is a novel molecular target for lowering intraocular pressure.

Role of the autotaxin-lysophosphatidic acid axis in glaucoma, aqueous humor drainage and fibrogenic activity.